Variant chr2-86790452-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001768.7(CD8A):c.279G>A(p.Arg93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,614,066 control chromosomes in the GnomAD database, including 4,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 406 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4115 hom. )

Consequence

CD8A
NM_001768.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.158

Variant links:

Genes affected

CD8A (HGNC:1706): (CD8 subunit alpha) 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 acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as 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 alpha chain. Multiple transcript variants encoding different isoforms have been found for this gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain and thus differ in being a membrane-anchored or secreted protein. [provided by RefSeq, May 2020]

CD8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-86790452-C-T is Benign according to our data. Variant chr2-86790452-C-T is described in ClinVar as [Benign]. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD8A	NM_001768.7 linkuse as main transcript	c.279G>A	p.Arg93=	synonymous_variant	2/6	ENST00000283635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD8A	ENST00000283635.8 linkuse as main transcript	c.279G>A	p.Arg93=	synonymous_variant	2/6	1	NM_001768.7	P1	P01732-1

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10620

AN:

152200

Hom.:

406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0673

GnomAD3 exomes

AF:

0.0573

AC:

14392

AN:

250974

Hom.:

532

AF XY:

0.0561

AC XY:

7622

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0585

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0589

Gnomad NFE exome

AF:

0.0803

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0714

AC:

104343

AN:

1461748

Hom.:

4115

Cov.:

AF XY:

0.0699

AC XY:

50815

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0830

Gnomad4 AMR exome

AF:

0.0360

Gnomad4 ASJ exome

AF:

0.0561

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.0587

Gnomad4 NFE exome

AF:

0.0805

Gnomad4 OTH exome

AF:

0.0636

GnomAD4 genome

AF:

0.0698

AC:

10631

AN:

152318

Hom.:

406

Cov.:

AF XY:

0.0671

AC XY:

5001

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0832

Gnomad4 AMR

AF:

0.0469

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0578

Gnomad4 NFE

AF:

0.0787

Gnomad4 OTH

AF:

0.0666

Alfa

AF:

0.0562

Hom.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0767

EpiControl

AF:

0.0801

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.6

DANN

Benign

0.65

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

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