rs6547705

Positions:

• chr2-86817193-G-A
• chr2-86817193-G-C
• chr2-86817193-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172213.5(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 NM_172213.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

LOC105374846 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD8B	NM_172213.5	c.621-1475C>T		intron_variant			NP_757362.1
CD8B	NM_172101.5	c.*9-1475C>T		intron_variant			NP_742099.1
CD8B	NM_172102.5	c.531-1475C>T		intron_variant			NP_742100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8B	ENST00000331469.6	c.621-1475C>T		intron_variant		1		ENSP00000331172.2
CD8B	ENST00000393759.6	c.*9-1475C>T		intron_variant		1		ENSP00000377356.2
CD8B	ENST00000349455.7	c.531-1475C>T		intron_variant		1		ENSP00000340592.3
CD8B	ENST00000393761.6	c.494-1475C>T		intron_variant		1		ENSP00000377358.2

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

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.805

Alfa AF: 0.798 Hom.: 77046

Bravo AF: 0.846

Asia WGS AF: 0.815 AC: 2831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.17

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: rs6547705; hg19: chr2-87044316;