rs3020726

Variant names:

• chr2-86789383-A-G
• rs3020726
• NM_001768.7:c.565T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001768.7(CD8A):​c.565T>C​(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,118 control chromosomes in the GnomAD database, including 17,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1223 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15980 hom.)
• Consequence: CD8A NM_001768.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.163

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-86789383-A-G is Benign according to our data. Variant chr2-86789383-A-G is described in ClinVar as [Benign]. Clinvar id is 402521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.163 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD8A	NM_001768.7	c.565T>C	p.Leu189Leu	synonymous_variant	Exon 4 of 6	ENST00000283635.8	NP_001759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000283635.8	c.565T>C	p.Leu189Leu	synonymous_variant	Exon 4 of 6	1	NM_001768.7	ENSP00000283635.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18132 AN: 152042 Hom.: 1223 Cov.: 33

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.115 AC: 28955 AN: 251446 Hom.: 1960 AF XY: 0.115 AC XY: 15635 AN XY: 135914

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.0690

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0714

Gnomad SAS exome AF: 0.0542

Gnomad FIN exome AF: 0.0881

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.143 AC: 208915 AN: 1460958 Hom.: 15980 Cov.: 31 AF XY: 0.141 AC XY: 102303 AN XY: 726810

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.0719

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0598

Gnomad4 SAS exome AF: 0.0562

Gnomad4 FIN exome AF: 0.0914

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.119 AC: 18136 AN: 152160 Hom.: 1223 Cov.: 33 AF XY: 0.113 AC XY: 8415 AN XY: 74388

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0798

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.112

Alfa AF: 0.147 Hom.: 858

Bravo AF: 0.119

Asia WGS AF: 0.0630 AC: 219 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.154

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: Frequency -

Susceptibility to respiratory infections associated with CD8alpha chain mutation Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs3020726; hg19: chr2-87016506; COSMIC: COSV52157627;