rs708564

Variant names:

• chr11-2388869-C-T
• rs708564
• NM_004356.4:c.67-1543C>T

Variant summary

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

The NM_004356.4(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 NM_004356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 13 publications found

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]

CD81 Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency, common variable, 6

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004356.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	NM_004356.4	MANE Select	c.67-1543C>T		intron	N/A	NP_004347.1	P60033
	CD81	NM_001425135.1		c.67-1543C>T		intron	N/A	NP_001412064.1
	CD81	NM_001425137.1		c.67-1543C>T		intron	N/A	NP_001412066.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	ENST00000263645.10	TSL:1 MANE Select	c.67-1543C>T		intron	N/A	ENSP00000263645.5	P60033
	CD81	ENST00000533417.6	TSL:3	c.268-1543C>T		intron	N/A	ENSP00000435633.2	H0YEE2
	CD81	ENST00000381036.7	TSL:3	c.181-1543C>T		intron	N/A	ENSP00000370424.3	A6NMH8

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

African (AFR) AF: 0.315 AC: 13050 AN: 41492

American (AMR) AF: 0.604 AC: 9235 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2704 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2452 AN: 5148

South Asian (SAS) AF: 0.675 AC: 3255 AN: 4822

European-Finnish (FIN) AF: 0.645 AC: 6837 AN: 10608

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54295 AN: 67974

Other (OTH) AF: 0.666 AC: 1405 AN: 2110

Alfa AF: 0.727 Hom.: 92198

Bravo AF: 0.601

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.32
PhyloP100		-3.4
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: rs708564; hg19: chr11-2410099; COSMIC: COSV55133753; COSMIC: COSV55133753;