rs115370220

Variant names:

• chr2-86789707-C-A
• rs115370220
• NM_001768.7:c.447G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-86789707-C-A
• chr2-86789707-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001768.7(CD8A):​c.447G>T​(p.Ala149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000806 in 1,239,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A149A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: CD8A NM_001768.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 0 publications found

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]

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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.641 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001768.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8A	NM_001768.7	MANE Select	c.447G>T	p.Ala149Ala	synonymous	Exon 3 of 6	NP_001759.3
	CD8A	NM_001145873.1		c.447G>T	p.Ala149Ala	synonymous	Exon 6 of 9	NP_001139345.1
	CD8A	NM_001382698.1		c.447G>T	p.Ala149Ala	synonymous	Exon 5 of 8	NP_001369627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8A	ENST00000283635.8	TSL:1 MANE Select	c.447G>T	p.Ala149Ala	synonymous	Exon 3 of 6	ENSP00000283635.3
	CD8A	ENST00000409511.6	TSL:2	c.447G>T	p.Ala149Ala	synonymous	Exon 6 of 9	ENSP00000386559.2
	CD8A	ENST00000352580.7	TSL:2	c.447G>T	p.Ala149Ala	synonymous	Exon 3 of 5	ENSP00000321631.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.06e-7 AC: 1 AN: 1239948 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 604600

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25084

American (AMR) AF: 0.00 AC: 0 AN: 15954

Ashkenazi Jewish (ASJ) AF: 0.0000533 AC: 1 AN: 18778

East Asian (EAS) AF: 0.00 AC: 0 AN: 29492

South Asian (SAS) AF: 0.00 AC: 0 AN: 51774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012514

Other (OTH) AF: 0.00 AC: 0 AN: 51194

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism

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: rs115370220; hg19: chr2-87016830;