rs13023213

Positions:

• chr2-86794820-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145873.1(CD8A):​c.-270-3725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,148 control chromosomes in the GnomAD database, including 3,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3121 hom., cov: 32)
• Consequence: CD8A NM_001145873.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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]

LOC105374846 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD8A	NM_001145873.1	c.-270-3725A>G		intron_variant			NP_001139345.1
CD8A	NM_001382698.1	c.-270-3725A>G		intron_variant			NP_001369627.1
LOC105374846	XR_940321.3	n.844T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000409511.6	c.-270-3725A>G		intron_variant		2		ENSP00000386559.2
CD8A	ENST00000699439.1	c.-270-3725A>G		intron_variant				ENSP00000514390.1
CD8A	ENST00000699437.1	n.343-6260A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29441 AN: 152030 Hom.: 3118 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29460 AN: 152148 Hom.: 3121 Cov.: 32 AF XY: 0.186 AC XY: 13864 AN XY: 74376

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.186

Alfa AF: 0.214 Hom.: 767

Bravo AF: 0.189

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.34

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: rs13023213; hg19: chr2-87021943;