rs79392961

chr2-86790433-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001768.7(CD8A):c.298C>T(p.Leu100Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,138 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (38 hom.)
• Consequence: CD8A NM_001768.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009144366).
• BP6: Variant 2-86790433-G-A is Benign according to our data. Variant chr2-86790433-G-A is described in ClinVar as [Benign]. Clinvar id is 464446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1736/152326) while in subpopulation AFR AF= 0.0386 (1606/41576). AF 95% confidence interval is 0.0371. There are 38 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD8A	NM_001768.7	c.298C>T	p.Leu100Phe	missense_variant	2/6	ENST00000283635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD8A	ENST00000283635.8	c.298C>T	p.Leu100Phe	missense_variant	2/6	1	NM_001768.7	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1734 AN: 152208 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00301 AC: 756 AN: 251054 Hom.: 12 AF XY: 0.00222 AC XY: 302 AN XY: 135858

Gnomad AFR exome AF: 0.0422

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00129 AC: 1888 AN: 1461812 Hom.: 38 Cov.: 33 AF XY: 0.00110 AC XY: 802 AN XY: 727206

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.0114 AC: 1736 AN: 152326 Hom.: 38 Cov.: 33 AF XY: 0.0108 AC XY: 802 AN XY: 74480

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00222 Hom.: 13

Bravo AF: 0.0133

ESP6500AA AF: 0.0413 AC: 182

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00351 AC: 426

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.61	T;.;T;T
MetaRNN	Benign	0.0091	T;T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.7	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.46
MVP		0.99
MPC		1.4
ClinPred		0.027	T
GERP RS		4.7
Varity_R		0.78
gMVP		0.67

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: rs79392961; hg19: chr2-87017556;