rs4832054

Positions:

• chr2-86831457-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CD8B	NM_001178100.2	c.494-15739C>T		intron_variant			NP_001171571.1
CD8B	NM_172101.5	c.621-9083C>T		intron_variant			NP_742099.1
CD8B	NM_172102.5	c.530+13465C>T		intron_variant			NP_742100.1
CD8B	NM_172213.5	c.620+13465C>T		intron_variant			NP_757362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8B	ENST00000331469.6	c.620+13465C>T		intron_variant		1		ENSP00000331172	A2
CD8B	ENST00000349455.7	c.530+13465C>T		intron_variant		1		ENSP00000340592
CD8B	ENST00000393759.6	c.621-9083C>T		intron_variant		1		ENSP00000377356	A2
CD8B	ENST00000393761.6	c.494-15739C>T		intron_variant		1		ENSP00000377358

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

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0933

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.250

Alfa AF: 0.307 Hom.: 3431

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4832054; hg19: chr2-87058580;