Do not write out asterisk alleles (#18)

Closes: #18
Related-Issue: #18
Projected-Results-Impact: require-revalidation

CHANGES.md

@@ -8,6 +8,7 @@
 - Adding unit tests for `annotate` command (#31)
 - Adding unit tests for `annotate-sv` command (#33)
 - Writing out gzip-ed files if output file name ends in `.gz` (#11)
+- Do not write out asterisk alleles (#18)
 
 ## v0.21
 

varfish-annotator-cli/src/main/java/com/github/bihealth/varfish_annotator/annotate/AnnotateVcf.java

@@ -330,14 +330,17 @@ private void annotateVariantContext(
 
     final int numAlleles = ctx.getAlleles().size();
     for (int i = 1; i < numAlleles; ++i) {
+      // Skip allele if it is the asterisk allele.
+      final String baseString = ctx.getAlternateAllele(i - 1).getBaseString();
+      if ("*".equals(baseString)) {
+        continue;
+      }
+
       // Normalize the from the VCF (will probably pad variant to the left).
       final VariantDescription normalizedVar =
           normalizer.normalizeInsertion(
               new VariantDescription(
-                  contigName,
-                  ctx.getStart() - 1,
-                  ctx.getReference().getBaseString(),
-                  ctx.getAlternateAllele(i - 1).getBaseString()));
+                  contigName, ctx.getStart() - 1, ctx.getReference().getBaseString(), baseString));
 
       // Get annotations sorted descendingly by variant effect.
       final List<Annotation> sortedRefseqAnnos = sortAnnos(refseqAnnotationsList, i);

varfish-annotator-cli/src/test/java/com/github/bihealth/varfish_annotator/annotate/AnnotateGatkHcVcf37Test.java

@@ -9,6 +9,7 @@
 import org.apache.commons.io.FileUtils;
 import org.junit.jupiter.api.Assertions;
 import org.junit.jupiter.api.BeforeEach;
+import org.junit.jupiter.api.Test;
 import org.junit.jupiter.api.io.TempDir;
 import org.junit.jupiter.params.ParameterizedTest;
 import org.junit.jupiter.params.provider.ValueSource;
@@ -141,4 +142,25 @@ void testWithTrio(boolean gzipOutput) throws IOException {
             + "GRCh37\t1\t1\t981952\t981952\t592\tC\tT\tsnv\t.\t.\t{}\t{\"\"\"NA12878\"\"\":{\"\"\"gt\"\"\":\"\"\"0/1\"\"\",\"\"\"ad\"\"\":4,\"\"\"dp\"\"\":5,\"\"\"gq\"\"\":23},\"\"\"NA12891\"\"\":{\"\"\"gt\"\"\":\"\"\"0/0\"\"\",\"\"\"ad\"\"\":0,\"\"\"dp\"\"\":1,\"\"\"gq\"\"\":3},\"\"\"NA12892\"\"\":{\"\"\"gt\"\"\":\"\"\"0/1\"\"\",\"\"\"ad\"\"\":3,\"\"\"dp\"\"\":6,\"\"\"gq\"\"\":99}}\t0\t1\t2\t0\t0\tTRUE\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t148398\tNM_152486.2\tTRUE\t.\t.\t{\"intergenic_variant\"}\t101991\tENSG00000187634\tENST00000341065.4\tTRUE\t.\t.\t{\"intergenic_variant\"}\t101997\n";
     runTest("bwa.gatk_hc.NA12878.vcf.gz", "input/grch37", expectedDbInfo, expectedGts, gzipOutput);
   }
+
+  @Test
+  void testWithAsteriskAllele() throws IOException {
+    final String expectedDbInfo =
+        "genomebuild\tdb_name\trelease\n"
+            + "GRCh37\tclinvar\ttoday\n"
+            + "GRCh37\texac\tr1.0\n"
+            + "GRCh37\tgnomad_exomes\tr2.1.1\n"
+            + "GRCh37\tgnomad_genomes\tr2.1.1\n"
+            + "GRCh37\thgmd_public\tensembl_r104\n"
+            + "GRCh37\tthousand_genomes\tv5b.20130502\n";
+    final String expectedGts =
+        "release\tchromosome\tchromosome_no\tstart\tend\tbin\treference\talternative\tvar_type\tcase_id\tset_id\tinfo\tgenotype\tnum_hom_alt\tnum_hom_ref\tnum_het\tnum_hemi_alt\tnum_hemi_ref\tin_clinvar\texac_frequency\texac_homozygous\texac_heterozygous\texac_hemizygous\tthousand_genomes_frequency\tthousand_genomes_homozygous\tthousand_genomes_heterozygous\tthousand_genomes_hemizygous\tgnomad_exomes_frequency\tgnomad_exomes_homozygous\tgnomad_exomes_heterozygous\tgnomad_exomes_hemizygous\tgnomad_genomes_frequency\tgnomad_genomes_homozygous\tgnomad_genomes_heterozygous\tgnomad_genomes_hemizygous\trefseq_gene_id\trefseq_transcript_id\trefseq_transcript_coding\trefseq_hgvs_c\trefseq_hgvs_p\trefseq_effect\trefseq_exon_dist\tensembl_gene_id\tensembl_transcript_id\tensembl_transcript_coding\tensembl_hgvs_c\tensembl_hgvs_p\tensembl_effect\tensembl_exon_dist\n"
+            + "GRCh37\t1\t1\t981952\t981952\t592\tC\tT\tsnv\t.\t.\t{}\t{\"\"\"HG00102\"\"\":{\"\"\"gt\"\"\":\"\"\"0/1\"\"\",\"\"\"ad\"\"\":3,\"\"\"dp\"\"\":6,\"\"\"gq\"\"\":99}}\t0\t0\t1\t0\t0\tTRUE\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t0\t148398\tNM_152486.2\tTRUE\t.\t.\t{\"intergenic_variant\"}\t101991\tENSG00000187634\tENST00000341065.4\tTRUE\t.\t.\t{\"intergenic_variant\"}\t101997\n";
+    runTest(
+        "bwa.gatk_hc.HG00102.asterisk_alleles.vcf.gz",
+        "input/grch37",
+        expectedDbInfo,
+        expectedGts,
+        false);
+  }
 }

varfish-annotator-cli/src/test/resources/input/grch37/bwa.gatk_hc.HG00102.asterisk_alleles.vcf

@@ -0,0 +1,122 @@
+##fileformat=VCFv4.3
+##FILTER=<ID=PASS,Description="All filters passed">
+##FILTER=<ID=LowQual,Description="Low quality">
+##FORMAT=<ID=AD,Number=R,Type=Integer,Description="Allelic depths for the ref and alt alleles in the order listed">
+##FORMAT=<ID=DP,Number=1,Type=Integer,Description="Approximate read depth (reads with MQ=255 or with bad mates are filtered)">
+##FORMAT=<ID=GQ,Number=1,Type=Integer,Description="Genotype Quality">
+##FORMAT=<ID=GT,Number=1,Type=String,Description="Genotype">
+##FORMAT=<ID=PL,Number=G,Type=Integer,Description="Normalized, Phred-scaled likelihoods for genotypes as defined in the VCF specification">
+##GATKCommandLine.HaplotypeCaller=<ID=HaplotypeCaller,Version=3.7-0-gcfedb67,Date="Wed Sep 18 14:06:27 CEST 2019",Epoch=1568808387440,CommandLineOptions="analysis_type=HaplotypeCaller input_file=[/fast/work/groups/cubi/projects/2019-09-17_varfish_demo_data/GRCh37/ngs_mapping/work/bwa.HG00102/out/bwa.HG00102.bam] showFullBamList=false read_buffer_size=null read_filter=[] disable_read_filter=[] intervals=[1:1-50,010,000] excludeIntervals=null interval_set_rule=UNION interval_merging=ALL interval_padding=0 reference_sequence=/fast/projects/cubit/current/static_data/reference/GRCh37/hs37d5/hs37d5.fa nonDeterministicRandomSeed=false disableDithering=false maxRuntime=-1 maxRuntimeUnits=MINUTES downsampling_type=BY_SAMPLE downsample_to_fraction=null downsample_to_coverage=500 baq=OFF baqGapOpenPenalty=40.0 refactor_NDN_cigar_string=false fix_misencoded_quality_scores=false allow_potentially_misencoded_quality_scores=false useOriginalQualities=false defaultBaseQualities=-1 performanceLog=null BQSR=null quantize_quals=0 static_quantized_quals=null round_down_quantized=false disable_indel_quals=false emit_original_quals=false preserve_qscores_less_than=6 globalQScorePrior=-1.0 secondsBetweenProgressUpdates=10 validation_strictness=SILENT remove_program_records=false keep_program_records=false sample_rename_mapping_file=null unsafe=null disable_auto_index_creation_and_locking_when_reading_rods=false no_cmdline_in_header=false sites_only=false never_trim_vcf_format_field=false bcf=false bam_compression=null simplifyBAM=false disable_bam_indexing=false generate_md5=false num_threads=1 num_cpu_threads_per_data_thread=1 num_io_threads=0 monitorThreadEfficiency=false num_bam_file_handles=null read_group_black_list=null pedigree=[] pedigreeString=[] pedigreeValidationType=STRICT allow_intervals_with_unindexed_bam=false generateShadowBCF=false variant_index_type=DYNAMIC_SEEK variant_index_parameter=-1 reference_window_stop=0 phone_home= gatk_key=null tag=NA logging_level=INFO log_to_file=null help=false version=false out=/fast/users/holtgrem_c/scratch/tmp/tmp.San1J5p2CT/tmp.vcf.gz likelihoodCalculationEngine=PairHMM heterogeneousKmerSizeResolution=COMBO_MIN dbsnp=(RodBinding name=dbsnp source=/fast/projects/cubit/current/static_data/db/dbSNP/b147/GRCh37/All_20160408.vcf.gz) dontTrimActiveRegions=false maxDiscARExtension=25 maxGGAARExtension=300 paddingAroundIndels=150 paddingAroundSNPs=20 comp=[] annotation=[] excludeAnnotation=[] group=[StandardAnnotation, StandardHCAnnotation] debug=false useFilteredReadsForAnnotations=false emitRefConfidence=NONE bamOutput=null bamWriterType=CALLED_HAPLOTYPES emitDroppedReads=false disableOptimizations=false annotateNDA=false useNewAFCalculator=false heterozygosity=0.001 indel_heterozygosity=1.25E-4 heterozygosity_stdev=0.01 standard_min_confidence_threshold_for_calling=10.0 standard_min_confidence_threshold_for_emitting=30.0 max_alternate_alleles=6 max_genotype_count=1024 max_num_PL_values=100 input_prior=[] sample_ploidy=2 genotyping_mode=DISCOVERY alleles=(RodBinding name= source=UNBOUND) contamination_fraction_to_filter=0.0 contamination_fraction_per_sample_file=null p_nonref_model=null exactcallslog=null output_mode=EMIT_VARIANTS_ONLY allSitePLs=false gcpHMM=10 pair_hmm_implementation=VECTOR_LOGLESS_CACHING pair_hmm_sub_implementation=ENABLE_ALL always_load_vector_logless_PairHMM_lib=false phredScaledGlobalReadMismappingRate=45 noFpga=false sample_name=null kmerSize=[10, 25] dontIncreaseKmerSizesForCycles=false allowNonUniqueKmersInRef=false numPruningSamples=1 recoverDanglingHeads=false doNotRecoverDanglingBranches=false minDanglingBranchLength=4 consensus=false maxNumHaplotypesInPopulation=128 errorCorrectKmers=false minPruning=3 debugGraphTransformations=false allowCyclesInKmerGraphToGeneratePaths=false graphOutput=null kmerLengthForReadErrorCorrection=25 minObservationsForKmerToBeSolid=20 GVCFGQBands=[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 70, 80, 90, 99] indelSizeToEliminateInRefModel=10 min_base_quality_score=10 includeUmappedReads=false useAllelesTrigger=false doNotRunPhysicalPhasing=true keepRG=null justDetermineActiveRegions=false dontGenotype=false dontUseSoftClippedBases=false captureAssemblyFailureBAM=false errorCorrectReads=false pcr_indel_model=CONSERVATIVE maxReadsInRegionPerSample=10000 minReadsPerAlignmentStart=10 mergeVariantsViaLD=false activityProfileOut=null activeRegionOut=null activeRegionIn=null activeRegionExtension=null forceActive=false activeRegionMaxSize=null bandPassSigma=null maxReadsInMemoryPerSample=30000 maxTotalReadsInMemory=10000000 maxProbPropagationDistance=50 activeProbabilityThreshold=0.002 min_mapping_quality_score=20 filter_reads_with_N_cigar=false filter_mismatching_base_and_quals=false filter_bases_not_stored=false">
+##INFO=<ID=AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed">
+##INFO=<ID=AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed">
+##INFO=<ID=AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes">
+##INFO=<ID=BaseQRankSum,Number=1,Type=Float,Description="Z-score from Wilcoxon rank sum test of Alt Vs. Ref base qualities">
+##INFO=<ID=ClippingRankSum,Number=1,Type=Float,Description="Z-score From Wilcoxon rank sum test of Alt vs. Ref number of hard clipped bases">
+##INFO=<ID=DB,Number=0,Type=Flag,Description="dbSNP Membership">
+##INFO=<ID=DP,Number=1,Type=Integer,Description="Approximate read depth; some reads may have been filtered">
+##INFO=<ID=DS,Number=0,Type=Flag,Description="Were any of the samples downsampled?">
+##INFO=<ID=ExcessHet,Number=1,Type=Float,Description="Phred-scaled p-value for exact test of excess heterozygosity">
+##INFO=<ID=FS,Number=1,Type=Float,Description="Phred-scaled p-value using Fisher's exact test to detect strand bias">
+##INFO=<ID=HaplotypeScore,Number=1,Type=Float,Description="Consistency of the site with at most two segregating haplotypes">
+##INFO=<ID=InbreedingCoeff,Number=1,Type=Float,Description="Inbreeding coefficient as estimated from the genotype likelihoods per-sample when compared against the Hardy-Weinberg expectation">
+##INFO=<ID=MLEAC,Number=A,Type=Integer,Description="Maximum likelihood expectation (MLE) for the allele counts (not necessarily the same as the AC), for each ALT allele, in the same order as listed">
+##INFO=<ID=MLEAF,Number=A,Type=Float,Description="Maximum likelihood expectation (MLE) for the allele frequency (not necessarily the same as the AF), for each ALT allele, in the same order as listed">
+##INFO=<ID=MQ,Number=1,Type=Float,Description="RMS Mapping Quality">
+##INFO=<ID=MQRankSum,Number=1,Type=Float,Description="Z-score From Wilcoxon rank sum test of Alt vs. Ref read mapping qualities">
+##INFO=<ID=QD,Number=1,Type=Float,Description="Variant Confidence/Quality by Depth">
+##INFO=<ID=ReadPosRankSum,Number=1,Type=Float,Description="Z-score from Wilcoxon rank sum test of Alt vs. Ref read position bias">
+##INFO=<ID=SOR,Number=1,Type=Float,Description="Symmetric Odds Ratio of 2x2 contingency table to detect strand bias">
+##contig=<ID=1,length=249250621>
+##contig=<ID=2,length=243199373>
+##contig=<ID=3,length=198022430>
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+##contig=<ID=GL000192.1,length=547496>
+##contig=<ID=NC_007605,length=171823>
+##contig=<ID=hs37d5,length=35477943>
+##reference=file:///fast/projects/cubit/current/static_data/reference/GRCh37/hs37d5/hs37d5.fa
+##bcftools_viewVersion=1.9+htslib-1.9
+##bcftools_viewCommand=view --header-only /fast/users/holtgrem_c/scratch/tmp/tmp.San1J5p2CT/tmp.vcf.gz; Date=Wed Sep 18 14:09:14 2019
+##SAMPLE=<ID=HG00102,Sex=Female,Disease=Affected>
+##PEDIGREE=<ID=HG00102,Family=FAM_HG00102,Father=0,Mother=0>
+#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO	FORMAT	HG00102
+1	877769	.	C	*	2887.77	.	AC=2;AF=1;AN=2;DB;DP=65;ExcessHet=3.0103;FS=0;MLEAC=2;MLEAF=1;MQ=48.92;QD=29.09;SOR=1	GT:AD:DP:GQ:PL	0/1:0,65:65:99:2916,196,0
+1	981952	.	C	T,*	104.28	.	AC=2;AF=1;AN=2;DB;DP=3;ExcessHet=3.0103;FS=0;MLEAC=2;MLEAF=1;MQ=56.57;QD=34.76;SOR=1.179	GT:AD:DP:GQ:PL	1/2:0,3,3:6:99:437,228,239,110,0,204