rs10645

Variant names:

• chr11-2396906-C-G
• rs10645
• ENST00000531840.1:n.4745C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000531840.1(CD81):​n.4745C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,592,282 control chromosomes in the GnomAD database, including 214 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 0.0098 (9 hom., cov: 33)
  • Exomes 𝑓: 0.015 (205 hom.)
• Consequence: CD81 ENST00000531840.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 5 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: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00977 (1488/152348) while in subpopulation NFE AF = 0.0169 (1151/68022). AF 95% confidence interval is 0.0161. There are 9 homozygotes in GnomAd4. There are 665 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD81	NM_004356.4	c.*40C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000263645.10	NP_004347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.*40C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_004356.4	ENSP00000263645.5

Frequencies

GnomAD3 genomes AF: 0.00977 AC: 1488 AN: 152230 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.0102 AC: 2504 AN: 245942 AF XY: 0.0101

Gnomad AFR exome AF: 0.00229

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00524

Gnomad NFE exome AF: 0.0174

Gnomad OTH exome AF: 0.0100

GnomAD4 exome AF: 0.0153 AC: 22003 AN: 1439934 Hom.: 205 Cov.: 26 AF XY: 0.0149 AC XY: 10661 AN XY: 717572

African (AFR) AF: 0.00188 AC: 62 AN: 33020

American (AMR) AF: 0.00435 AC: 194 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 28 AN: 25984

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39544

South Asian (SAS) AF: 0.00756 AC: 649 AN: 85804

European-Finnish (FIN) AF: 0.00571 AC: 288 AN: 50402

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5736

European-Non Finnish (NFE) AF: 0.0183 AC: 20030 AN: 1095096

Other (OTH) AF: 0.0124 AC: 739 AN: 59730

GnomAD4 genome AF: 0.00977 AC: 1488 AN: 152348 Hom.: 9 Cov.: 33 AF XY: 0.00893 AC XY: 665 AN XY: 74494

African (AFR) AF: 0.00303 AC: 126 AN: 41588

American (AMR) AF: 0.00549 AC: 84 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.00518 AC: 55 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0169 AC: 1151 AN: 68022

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0106 Hom.: 2

Bravo AF: 0.00964

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs10645; hg19: chr11-2418136;