rs2019938

Variant names:

• chr11-2381517-A-G
• rs2019938
• NM_004356.4:c.66+3902A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 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.66+3902A>G		intron	N/A	NP_004347.1	P60033
	CD81	NM_001425135.1		c.66+3902A>G		intron	N/A	NP_001412064.1
	CD81	NM_001425137.1		c.66+3902A>G		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.66+3902A>G		intron	N/A	ENSP00000263645.5	P60033
	CD81	ENST00000533417.6	TSL:3	c.267+2311A>G		intron	N/A	ENSP00000435633.2	H0YEE2
	CD81	ENST00000905044.1		c.66+3902A>G		intron	N/A	ENSP00000575103.1

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

African (AFR) AF: 0.444 AC: 18408 AN: 41502

American (AMR) AF: 0.641 AC: 9807 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2735 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2328 AN: 5176

South Asian (SAS) AF: 0.676 AC: 3266 AN: 4828

European-Finnish (FIN) AF: 0.646 AC: 6840 AN: 10582

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54172 AN: 68022

Other (OTH) AF: 0.698 AC: 1476 AN: 2114

Alfa AF: 0.753 Hom.: 146781

Bravo AF: 0.646

Asia WGS AF: 0.595 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.60
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2019938; hg19: chr11-2402747;