rs13023213

Variant names:

• chr2-86794820-T-C
• rs13023213
• XR_940321.3:n.844T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_940321.3(LOC105374846):​n.844T>C variant causes a non coding transcript exon 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: LOC105374846 XR_940321.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 10 publications found

Genes affected

LOC105374846 (HGNC:):

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 Gene-Disease associations (from GenCC):

• susceptibility to respiratory infections associated with CD8alpha chain mutation

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC105374846	XR_940321.3	n.844T>C		non_coding_transcript_exon_variant	Exon 1 of 3
LOC105374846	XR_940322.3	n.844T>C		non_coding_transcript_exon_variant	Exon 1 of 3
CD8A	NM_001145873.1	c.-270-3725A>G		intron_variant	Intron 3 of 8		NP_001139345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000409511.6	c.-270-3725A>G		intron_variant	Intron 3 of 8	2		ENSP00000386559.2
CD8A	ENST00000699439.1	c.-270-3725A>G		intron_variant	Intron 2 of 6			ENSP00000514390.1
CD8A	ENST00000699437.1	n.343-6260A>G		intron_variant	Intron 2 of 3

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

African (AFR) AF: 0.151 AC: 6249 AN: 41518

American (AMR) AF: 0.135 AC: 2059 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3470

East Asian (EAS) AF: 0.0692 AC: 358 AN: 5176

South Asian (SAS) AF: 0.0644 AC: 311 AN: 4828

European-Finnish (FIN) AF: 0.171 AC: 1816 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17301 AN: 67968

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.212 Hom.: 773

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
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13023213; hg19: chr2-87021943;