Genetic Variant CD8B:p.Ala190Ser (chr2-86846699-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004931.5(CD8B):c.568G>T(p.Ala190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A190T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CD8B
NM_004931.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4056112).

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.568G>T	p.Ala190Ser	missense	Exon 4 of 6	NP_004922.1	P10966-1
CD8B	NM_172213.5		c.568G>T	p.Ala190Ser	missense	Exon 4 of 6	NP_757362.1	P10966-6
CD8B	NM_172101.5		c.568G>T	p.Ala190Ser	missense	Exon 4 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.568G>T	p.Ala190Ser	missense	Exon 4 of 6	ENSP00000375070.6	P10966-1
CD8B	ENST00000331469.6	TSL:1	c.568G>T	p.Ala190Ser	missense	Exon 4 of 6	ENSP00000331172.2	P10966-6
CD8B	ENST00000393759.6	TSL:1	c.568G>T	p.Ala190Ser	missense	Exon 4 of 7	ENSP00000377356.2	P10966-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1424514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705254

African (AFR)

AF:

0.00

AC:

AN:

32728

American (AMR)

AF:

0.00

AC:

AN:

39206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25380

East Asian (EAS)

AF:

0.00

AC:

AN:

38116

South Asian (SAS)

AF:

0.00

AC:

AN:

81068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092180

Other (OTH)

AF:

0.00

AC:

AN:

58990

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.69

M_CAP

Benign

0.013

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.61

PhyloP100

1.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.91

REVEL

Benign

0.099

Sift

Uncertain

0.022

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.47

MutPred

0.28

Gain of sheet (P = 0.0344)

MVP

0.56

MPC

1.4

ClinPred

0.92

GERP RS

3.1

Varity_R

0.10

gMVP

0.24

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over