11-2377558-G-C

Variant names:

• chr11-2377558-G-C
• rs532332389
• NM_004356.4:c.9G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004356.4(CD81):​c.9G>C​(p.Val3Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000809 in 1,483,026 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (3 hom.)
• Consequence: CD81 NM_004356.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.623
• Publications: 0 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-AS1 (HGNC:49384): (CD81 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-2377558-G-C is Benign according to our data. Variant chr11-2377558-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1460443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.623 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,AD,Unknown gene

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.9G>C	p.Val3Val	synonymous	Exon 1 of 8	NP_004347.1	P60033
	CD81	NM_001425135.1		c.9G>C	p.Val3Val	synonymous	Exon 1 of 8	NP_001412064.1
	CD81	NM_001425137.1		c.9G>C	p.Val3Val	synonymous	Exon 1 of 8	NP_001412066.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD81	ENST00000263645.10	TSL:1 MANE Select	c.9G>C	p.Val3Val	synonymous	Exon 1 of 8	ENSP00000263645.5	P60033
	CD81-AS1	ENST00000427151.1	TSL:1	n.404+28C>G		intron	N/A
	CD81	ENST00000905044.1		c.9G>C	p.Val3Val	synonymous	Exon 4 of 11	ENSP00000575103.1

Frequencies

GnomAD3 genomes AF: 0.0000733 AC: 11 AN: 150008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000130 AC: 21 AN: 161838 AF XY: 0.000169

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000818 AC: 109 AN: 1332912 Hom.: 3 Cov.: 29 AF XY: 0.0000955 AC XY: 63 AN XY: 659624

African (AFR) AF: 0.00 AC: 0 AN: 27152

American (AMR) AF: 0.00 AC: 0 AN: 33230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22074

East Asian (EAS) AF: 0.00 AC: 0 AN: 29232

South Asian (SAS) AF: 0.00136 AC: 105 AN: 76970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4794

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040708

Other (OTH) AF: 0.0000565 AC: 3 AN: 53120

GnomAD4 genome AF: 0.0000733 AC: 11 AN: 150114 Hom.: 0 Cov.: 32 AF XY: 0.0000681 AC XY: 5 AN XY: 73380

African (AFR) AF: 0.00 AC: 0 AN: 41262

American (AMR) AF: 0.00 AC: 0 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67330

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CD81-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.56
PhyloP100		0.62
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs532332389; hg19: chr11-2398788;