Third sublineage in B.1.1.529 (Omicron-related)

[rambaut]

A new diverse genome has appeared within the B.1.1.529 lineage that has all of the shared mutations of B.1.1.529, some of the mutations unique to BA.1 and some unique to BA.2 plus a few of its own.

Name: England/MILK-2D24AC9/2021, accession EPI_ISL_7526186, collected 2021-12-03

It seems likely this is an additional circulating member of the B.1.1.529 diversity and that recombination has occurred in its history (although this is likely to have occurred prior to the emergence of the BA.1 clade based on the pattern of mutations).

As a single genome it doesn't yet require a lineage designation and at the moment it will be classified as a member of B.1.1.529.

[AngieHinrichs]

@amniewiadomska suggests these new sequences as well:

hCoV-19/South Africa/NICD-N22389/2021|EPI_ISL_7605590|2021-11-30
hCoV-19/South Africa/NICD-N22404/2021|EPI_ISL_7605591|2021-11-25
hCoV-19/South Africa/NICD-N22385/2021|EPI_ISL_7605772|2021-11-29
hCoV-19/South Africa/NICD-N22239/2021|EPI_ISL_7605589|2021-11-26
hCoV-19/South Africa/NICD-N22163/2021|EPI_ISL_7605713|2021-11-18

(posting on her behalf since comments are locked down)

[rambaut]

Yes - these are the same sub-lineage. A couple of the mutations listed above are unique to England/MILK-2D24AC9/2021 so will be removed from the defining list. But I think this qualifies as BA.3 now.

Table of mutations

mut (nuc)	gene	mutation (aa)	B.1.1.529	BA.1	BA.2	BA.3 (proposed)	notes
T670G	ORF1ab	S135R			Y	Y
C832T	nuc	C832T				Y
C2790T	ORF1ab	T842I			Y
A2832G	ORF1ab	K856R		Y
C3037T	nuc	C3037T	Y			Y	B.1
T5386G	nuc	T5386G		Y
G4184A	ORF1ab	G1307S			Y	Y
C4321T	nuc	C4321T			Y
6513_6515del	ORF1ab	SL2083I		Y
G8393A	ORF1ab	A2710T		Y
C9344T	ORF1ab	L3027F			Y
A9424G	nuc	A9424G			Y
C9534T	ORF1ab	T3090I			Y	Y
C9866T	ORF1ab	L3201F			Y		Not in CERI-KRISP-K032307
C10029T	ORF1ab	T3255I	Y			Y
C10198T	nuc	C10198T			Y
G10447A	nuc	G10447A			Y	Y
C10449A	ORF1ab	P3395H	Y			Y
C11235T	nuc	C11235T				Y
11288_11296del	ORF1ab	SGF3675del	Y			Y	The exact position of this deletion is ambigous in nucleotide coordinates
T11296G	ORF1ab	F3677L			Y	Y	depending on the position of the deletion
G11287T	ORF1ab	L3674F		Y			depending on the position of the deletion
A11537G	ORF1ab	I3758V		Y
C12880T	nuc	C12880T			Y	Y
C14408T	ORF1ab	P4715L	Y			Y	B.1
C15240T	nuc	C15240T		Y
C15714T	nuc	C15714T			Y	Y
C17410T	ORF1ab	R5716C			Y
A18163G	ORF1ab	I5967V	Y
C19955T	ORF1ab	T6564I			Y
A20055G	nuc	A20055G			Y
C21618T	S	T19I			Y
21633_21641del	S	LPPA24S			Y
C21762T	S	A67V		Y		Y
21765_21770del	S	HV69del		Y		Y
C21846T	S	T95I		Y
G21987A (outlier); 21987_21995 (main)	S	G142D	Y
21987_21995	S	VYY143del		Y		Y
22194_22196del	S	NL211I		Y		Y
T22200G	S	V213G			Y
22205GAGCCAGAAins	S	215EPEins		Y
G22578A	S	G339D	Y			Y
C22674T	S	S371F			Y	Y
T22673C, C22674T	S	S371L		Y
T22679C	S	S373P	Y			Y
C22686T	S	S375F	Y			Y
A22688G	S	T376A			Y
G22775A	S	D405N			Y	Y
A22786T	S	R408S			Y
G22813T	S	K417N	Y			Y
T22882G	S	N440K	Y			Y
G22898A	S	G446S		Y		Y
G22992A	S	S477N	Y			Y
C22995A	S	T478K	Y			Y
A23013C	S	E484A	Y			Y
A23040G	S	Q493R	Y			Y
G23048A	S	G496S		Y
A23055G	S	Q498R	Y			Y
A23063T	S	N501Y	Y			Y
T23075C	S	Y505H	Y			Y
C23202A	S	T547K		Y
A23403G	S	D614G	Y			Y	B.1
C23525T	S	H655Y	Y			Y
T23599G	S	N679K	Y			Y
C23604A	S	P681H	Y			Y
C23854A	S	N764K	Y			?
G23948T	S	D796Y	Y			Y
C24130A	S	N856K		Y
A24424T	S	Q954H	Y			Y
T24469A	S	N969K	Y			Y
C24503T	S	L981F		Y
C25000T	nuc	C25000T	Y
C25584T	nuc	C25584T	Y
A26059G,C26060T	ORF3a	T223V				Y	ACT->GTT
C26060T	ORF3a	T223I			Y		ACT->ATT (not fixed in BA.3)
C26270T	E	T9I	Y			Y
A26530G	M	D3G		Y			Not in CERI-KRISP-K032307
C26577G	M	Q19E	Y			Y
G26709A	M	A63T	Y			Y
C26858T	nuc	C26858T			Y	Y
A27259C	nuc	A27259C	Y			Y
G27382C, A27383T, T27384C	ORF6	D61L			Y		(GAT->CTC)
C27807T	nuc	C27807T	Y			Y
A28271T	nuc	A28271T	Y			Y
C28311T	N	P13L	Y			Y
28362_28370del	N	ERS31del	Y			Y
G28881A, G28882A, G28883C	N	RG203KR	Y			Y	(B.1.1.1)
A29510C	N	S413R			Y	Y

[chrisruis]

Now added as BA.3 in v1.2.112

[zach-hensel]

I don't think EPI_ISL_6906349 and EPI_ISL_4652284 qualify to be a sub-lineage but they might be worth reconsidering in light of overlap with all three of these in some places but only BA.1 in others, plus time/location information. I mentioned one of these elsewhere, but @c19850727 recently noted the additional one and also possibly related EPI_ISL_3838306.

[c19850727]

From @corneliusroemer: I copied this comment to its own issue, please discuss there: #455

@rambaut

Hi I came across the following 5 sequences:

Accession	Virus name
EPI_ISL_8262451	hCoV-19/USA/CO-CDC-MMB12218639/2021
EPI_ISL_8439638	hCoV-19/South Africa/NICD-N23764/2021
EPI_ISL_8402519	hCoV-19/Puerto Rico/PR-CDC-S874/2021
EPI_ISL_9962725	hCoV-19/South Africa/NICD-N29342/2022
EPI_ISL_10210515	hCoV-19/South Africa/NICD-N29407/2022

• They are all classified as BA.1 by Pango/Nextstrain, but with G2832A reversed.
• Instead, they have T670G (BA.2 and BA.3 defining ), C832T (BA.3 defining ), G4184A (BA.2 and BA.3 defining) and C4321T (BA.2 defining).
• Downstream from T5386G it's all BA.1, but with a few private mutations: G7684A, C29167T, G29734A.

[corneliusroemer]

@c19850727 Are these sequences all identical? Do they have many stretches of N or any signs of bad quality or artefacts?