rs1248329743

Variant names:

• chr2-86858282-C-T
• rs1248329743
• NM_004931.5:c.178G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004931.5(CD8B):​c.178G>A​(p.Ala60Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CD8B NM_004931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.233
• Publications: 0 publications found

Genes affected

CD8B (HGNC:1707): (CD8 subunit beta) The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]

ENSG00000291013 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1565249).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004931.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8B	NM_004931.5	MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 2 of 6	NP_004922.1	P10966-1
	CD8B	NM_172213.5		c.178G>A	p.Ala60Thr	missense	Exon 2 of 6	NP_757362.1	P10966-6
	CD8B	NM_172101.5		c.178G>A	p.Ala60Thr	missense	Exon 2 of 7	NP_742099.1	P10966-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8B	ENST00000390655.12	TSL:1 MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 2 of 6	ENSP00000375070.6	P10966-1
	CD8B	ENST00000331469.6	TSL:1	c.178G>A	p.Ala60Thr	missense	Exon 2 of 6	ENSP00000331172.2	P10966-6
	CD8B	ENST00000393759.6	TSL:1	c.178G>A	p.Ala60Thr	missense	Exon 2 of 7	ENSP00000377356.2	P10966-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152242 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461668 Hom.: 0 Cov.: 38 AF XY: 0.00000688 AC XY: 5 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111842

Other (OTH) AF: 0.0000331 AC: 2 AN: 60378

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152242 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.23
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.033
Sift	Benign	0.090	T
Sift4G	Uncertain	0.046	D
Polyphen		0.97	D
Vest4		0.15
MutPred		0.48		Gain of phosphorylation at A60 (P = 0.0502)
MVP		0.52
MPC		0.96
ClinPred		0.34	T
GERP RS		1.2
Varity_R		0.046
gMVP		0.39
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1248329743; hg19: chr2-87085405;