2-86853008-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004931.5(CD8B):c.482A>G(p.Glu161Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,536,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 29)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

CD8B
NM_004931.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.58

Publications

0 publications found

Variant links:

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]

CD8B links:

ENSG00000291013 (HGNC:):

ENSG00000291013 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03161457).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD8B	NM_004931.5	MANE Select	c.482A>G	p.Glu161Gly	missense	Exon 3 of 6	NP_004922.1	P10966-1
CD8B	NM_172213.5		c.482A>G	p.Glu161Gly	missense	Exon 3 of 6	NP_757362.1	P10966-6
CD8B	NM_172101.5		c.482A>G	p.Glu161Gly	missense	Exon 3 of 7	NP_742099.1	P10966-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD8B	ENST00000390655.12	TSL:1 MANE Select	c.482A>G	p.Glu161Gly	missense	Exon 3 of 6	ENSP00000375070.6	P10966-1
CD8B	ENST00000331469.6	TSL:1	c.482A>G	p.Glu161Gly	missense	Exon 3 of 6	ENSP00000331172.2	P10966-6
CD8B	ENST00000393759.6	TSL:1	c.482A>G	p.Glu161Gly	missense	Exon 3 of 7	ENSP00000377356.2	P10966-2

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000137

AC:

AN:

146314

AF XY:

0.0000257

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000866

AC:

AN:

1385632

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30656

American (AMR)

AF:

0.00

AC:

AN:

32714

Ashkenazi Jewish (ASJ)

AF:

0.000402

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

35602

South Asian (SAS)

AF:

0.00

AC:

AN:

78658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4354

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1072248

Other (OTH)

AF:

0.00

AC:

AN:

57318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150534

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40828

American (AMR)

AF:

0.00

AC:

AN:

15020

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5064

South Asian (SAS)

AF:

0.00

AC:

AN:

4692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67686

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.0030

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.078

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.51

M_CAP

Benign

0.0013

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.1

PhyloP100

-2.6

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.79

REVEL

Benign

0.0030

Sift

Benign

0.34

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.056

MutPred

0.19

Loss of sheet (P = 0.0357)

MVP

0.15

MPC

0.65

ClinPred

0.10

GERP RS

-8.9

Varity_R

0.047

gMVP

0.36

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over