11-2388869-C-T

Position:

• chr11-2388869-C-T

Variant summary

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

The ENST00000263645.10(CD81):​c.67-1543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,128 control chromosomes in the GnomAD database, including 32,473 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 0.62 (32473 hom., cov: 33)
• Consequence: CD81 ENST00000263645.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35

Genes affected

CD81 (HGNC:1701): (CD81 molecule) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This protein appears to promote muscle cell fusion and support myotube maintenance. Also it may be involved in signal transduction. This gene is localized in the tumor-suppressor gene region and thus it is a candidate gene for malignancies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD81	NM_004356.4	c.67-1543C>T		intron_variant		ENST00000263645.10	NP_004347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.67-1543C>T		intron_variant		1	NM_004356.4	ENSP00000263645	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94230 AN: 152010 Hom.: 32473 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.619 AC: 94241 AN: 152128 Hom.: 32473 Cov.: 33 AF XY: 0.612 AC XY: 45532 AN XY: 74362

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.666

Alfa AF: 0.770 Hom.: 54912

Bravo AF: 0.601

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.32

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: rs708564; hg19: chr11-2410099; COSMIC: COSV55133753; COSMIC: COSV55133753;