rs2019938

Positions:

• chr11-2381517-A-G

Variant summary

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

The NM_004356.4(CD81):​c.66+3902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,196 control chromosomes in the GnomAD database, including 34,697 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 0.66 (34697 hom., cov: 34)
• Consequence: CD81 NM_004356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD81	NM_004356.4	c.66+3902A>G		intron_variant		ENST00000263645.10	NP_004347.1
CD81	NM_001297649.2	c.-148+5160A>G		intron_variant			NP_001284578.1
CD81	XM_047427931.1	c.267+2311A>G		intron_variant			XP_047283887.1
CD81	XM_047427933.1	c.17+3270A>G		intron_variant			XP_047283889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD81	ENST00000263645.10	c.66+3902A>G		intron_variant		1	NM_004356.4	ENSP00000263645.5
CD81	ENST00000533417.6	c.267+2311A>G		intron_variant		3		ENSP00000435633.2
CD81	ENST00000475945.7	c.-148+5160A>G		intron_variant		2		ENSP00000433178.2
CD81	ENST00000530648.5	c.-148+4597A>G		intron_variant		4		ENSP00000432723.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100010 AN: 152078 Hom.: 34691 Cov.: 34

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.657 AC: 100048 AN: 152196 Hom.: 34697 Cov.: 34 AF XY: 0.649 AC XY: 48299 AN XY: 74396

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.698

Alfa AF: 0.779 Hom.: 60823

Bravo AF: 0.646

Asia WGS AF: 0.595 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2019938; hg19: chr11-2402747;