Variant 2-86858081-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_004931.5(CD8B):c.379G>A(p.Gly127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CD8B
NM_004931.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD8B	NM_004931.5 linkuse as main transcript	c.379G>A	p.Gly127Arg	missense_variant	2/6	ENST00000390655.12	NP_004922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8B	ENST00000390655.12 linkuse as main transcript	c.379G>A	p.Gly127Arg	missense_variant	2/6	1	NM_004931.5	ENSP00000375070	P4	P10966-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251098

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.379G>A (p.G127R) alteration is located in exon 2 (coding exon 2) of the CD8B gene. This alteration results from a G to A substitution at nucleotide position 379, causing the glycine (G) at amino acid position 127 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

.;.;.;.;D;T

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Uncertain

0.18

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-7.7

D;D;D;D;D;.

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

D;D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

.;D;D;D;D;.

Vest4

0.71

MutPred

0.91

Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);

MVP

0.89

MPC

1.7

ClinPred

1.0

GERP RS

3.7

Varity_R

0.69

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over