2-86817193-G-A

Variant names:

• chr2-86817193-G-A
• rs6547705
• ENST00000331469.6:c.621-1475C>T

Variant summary

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

The ENST00000331469.6(CD8B):​c.621-1475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,160 control chromosomes in the GnomAD database, including 53,010 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 0.83 (53010 hom., cov: 32)
• Consequence: CD8B ENST00000331469.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 23 publications found

Genes affected

CD8B (HGNC:1707): (CD8 subunit beta) 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, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or 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 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]

ENSG00000291013 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000331469.6. 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
	CD8B	NM_172213.5		c.621-1475C>T		intron	N/A	NP_757362.1
	CD8B	NM_172101.5		c.*9-1475C>T		intron	N/A	NP_742099.1
	CD8B	NM_172102.5		c.531-1475C>T		intron	N/A	NP_742100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8B	ENST00000331469.6	TSL:1	c.621-1475C>T		intron	N/A	ENSP00000331172.2
	CD8B	ENST00000393759.6	TSL:1	c.*9-1475C>T		intron	N/A	ENSP00000377356.2
	CD8B	ENST00000349455.7	TSL:1	c.531-1475C>T		intron	N/A	ENSP00000340592.3

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126136 AN: 152042 Hom.: 52947 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.830 AC: 126262 AN: 152160 Hom.: 53010 Cov.: 32 AF XY: 0.822 AC XY: 61112 AN XY: 74368

African (AFR) AF: 0.946 AC: 39315 AN: 41542

American (AMR) AF: 0.779 AC: 11906 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2505 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5103 AN: 5188

South Asian (SAS) AF: 0.622 AC: 2999 AN: 4818

European-Finnish (FIN) AF: 0.746 AC: 7872 AN: 10554

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53897 AN: 67990

Other (OTH) AF: 0.805 AC: 1701 AN: 2114

Alfa AF: 0.806 Hom.: 175124

Bravo AF: 0.846

Asia WGS AF: 0.815 AC: 2831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.17
PhyloP100		-1.3
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: rs6547705; hg19: chr2-87044316;