rs181102668

chr2-86790560-G-Achr2-86790560-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001768.7(CD8A):c.171C>T(p.Leu57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,613,344 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L57L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0045 (23 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (48 hom.)
• Consequence: CD8A NM_001768.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.188

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-86790560-G-A is Benign according to our data. Variant chr2-86790560-G-A is described in ClinVar as [Benign]. Clinvar id is 533088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.188 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00451 (687/152342) while in subpopulation AMR AF= 0.0426 (652/15306). AF 95% confidence interval is 0.0399. There are 23 homozygotes in gnomad4. There are 428 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD8A	NM_001768.7	c.171C>T	p.Leu57=	synonymous_variant	2/6	ENST00000283635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD8A	ENST00000283635.8	c.171C>T	p.Leu57=	synonymous_variant	2/6	1	NM_001768.7	P1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 684 AN: 152224 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00379 AC: 931 AN: 245882 Hom.: 33 AF XY: 0.00287 AC XY: 384 AN XY: 133894

Gnomad AFR exome AF: 0.000322

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000495

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000547

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.000956 AC: 1396 AN: 1461002 Hom.: 48 Cov.: 34 AF XY: 0.000830 AC XY: 603 AN XY: 726842

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00451 AC: 687 AN: 152342 Hom.: 23 Cov.: 33 AF XY: 0.00575 AC XY: 428 AN XY: 74496

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.0426

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.00578

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	8.3
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs181102668; hg19: chr2-87017683; COSMIC: COSV52157222;