rs147048705

Variant names:

• chr2-86790578-C-A
• rs147048705
• NM_001768.7:c.153G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-86790578-C-A
• chr2-86790578-C-G
• chr2-86790578-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001768.7(CD8A):​c.153G>T​(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,612,602 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (28 hom.)
• Consequence: CD8A NM_001768.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.22
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-86790578-C-A is Benign according to our data. Variant chr2-86790578-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 464445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.22 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8A	NM_001768.7	MANE Select	c.153G>T	p.Thr51Thr	synonymous	Exon 2 of 6	NP_001759.3
	CD8A	NM_001145873.1		c.153G>T	p.Thr51Thr	synonymous	Exon 5 of 9	NP_001139345.1	Q6ZVS2
	CD8A	NM_001382698.1		c.153G>T	p.Thr51Thr	synonymous	Exon 4 of 8	NP_001369627.1	P01732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8A	ENST00000283635.8	TSL:1 MANE Select	c.153G>T	p.Thr51Thr	synonymous	Exon 2 of 6	ENSP00000283635.3	P01732-1
	CD8A	ENST00000409511.6	TSL:2	c.153G>T	p.Thr51Thr	synonymous	Exon 5 of 9	ENSP00000386559.2	P01732-1
	CD8A	ENST00000352580.7	TSL:2	c.153G>T	p.Thr51Thr	synonymous	Exon 2 of 5	ENSP00000321631.3	P01732-2

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152178 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00310 AC: 759 AN: 244788 AF XY: 0.00312

Gnomad AFR exome AF: 0.000835

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.000703

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00582

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00534 AC: 7802 AN: 1460306 Hom.: 28 Cov.: 34 AF XY: 0.00524 AC XY: 3809 AN XY: 726522

African (AFR) AF: 0.00102 AC: 34 AN: 33476

American (AMR) AF: 0.000514 AC: 23 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00114 AC: 98 AN: 86234

European-Finnish (FIN) AF: 0.00156 AC: 81 AN: 52070

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00657 AC: 7310 AN: 1111890

Other (OTH) AF: 0.00399 AC: 241 AN: 60368

GnomAD4 genome AF: 0.00305 AC: 464 AN: 152296 Hom.: 2 Cov.: 33 AF XY: 0.00279 AC XY: 208 AN XY: 74474

African (AFR) AF: 0.00127 AC: 53 AN: 41582

American (AMR) AF: 0.00183 AC: 28 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00538 AC: 366 AN: 68006

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00418 Hom.: 0

Bravo AF: 0.00300

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00545

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CD8A-related disorder (1)
-	-	1	Susceptibility to respiratory infections associated with CD8alpha chain mutation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.80
DANN	Benign	0.65
PhyloP100		-3.2
PromoterAI		0.038	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147048705; hg19: chr2-87017701;