rs4832054

Variant names:

• chr2-86831457-G-A
• rs4832054
• ENST00000331469.6:c.620+13465C>T

Variant summary

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

The ENST00000331469.6(CD8B):​c.620+13465C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,182 control chromosomes in the GnomAD database, including 5,858 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 0.27 (5858 hom., cov: 32)
• Consequence: CD8B ENST00000331469.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD8B	NM_172213.5	c.620+13465C>T		intron_variant	Intron 5 of 5		NP_757362.1
CD8B	NM_172101.5	c.621-9083C>T		intron_variant	Intron 5 of 6		NP_742099.1
CD8B	NM_172102.5	c.530+13465C>T		intron_variant	Intron 4 of 4		NP_742100.1
CD8B	NM_001178100.2	c.494-15739C>T		intron_variant	Intron 3 of 3		NP_001171571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD8B	ENST00000331469.6	c.620+13465C>T		intron_variant	Intron 5 of 5	1		ENSP00000331172.2
CD8B	ENST00000393759.6	c.621-9083C>T		intron_variant	Intron 5 of 6	1		ENSP00000377356.2
CD8B	ENST00000349455.7	c.530+13465C>T		intron_variant	Intron 4 of 4	1		ENSP00000340592.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40569 AN: 152064 Hom.: 5859 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.267 AC: 40590 AN: 152182 Hom.: 5858 Cov.: 32 AF XY: 0.263 AC XY: 19531 AN XY: 74384

African (AFR) AF: 0.181 AC: 7533 AN: 41520

American (AMR) AF: 0.290 AC: 4431 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3468

East Asian (EAS) AF: 0.0933 AC: 484 AN: 5186

South Asian (SAS) AF: 0.180 AC: 868 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2862 AN: 10574

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22430 AN: 68002

Other (OTH) AF: 0.250 AC: 527 AN: 2112

Alfa AF: 0.309 Hom.: 3826

Bravo AF: 0.266

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.20
PhyloP100		-0.38
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: rs4832054; hg19: chr2-87058580;