Genetic Variant CD81:p.Val20Val (chr11-2377609-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_004356.4(CD81):c.60C>A(p.Val20Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V20V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CD81
NM_004356.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

0 publications found

Variant links:

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 links:

CD81-AS1 (HGNC:49384): (CD81 antisense RNA 1)

CD81-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP7

Synonymous conserved (PhyloP=1.83 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD81	NM_004356.4	MANE Select	c.60C>A	p.Val20Val	synonymous	Exon 1 of 8	NP_004347.1	P60033
CD81	NM_001425135.1		c.60C>A	p.Val20Val	synonymous	Exon 1 of 8	NP_001412064.1
CD81	NM_001425137.1		c.60C>A	p.Val20Val	synonymous	Exon 1 of 8	NP_001412066.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD81	ENST00000263645.10	TSL:1 MANE Select	c.60C>A	p.Val20Val	synonymous	Exon 1 of 8	ENSP00000263645.5	P60033
CD81-AS1	ENST00000427151.1	TSL:1	n.381G>T		non_coding_transcript_exon	Exon 1 of 3
CD81	ENST00000905044.1		c.60C>A	p.Val20Val	synonymous	Exon 4 of 11	ENSP00000575103.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.18e-7

AC:

AN:

1393404

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691740

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29356

American (AMR)

AF:

0.00

AC:

AN:

39120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24038

East Asian (EAS)

AF:

0.00

AC:

AN:

34334

South Asian (SAS)

AF:

0.00

AC:

AN:

80298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5442

European-Non Finnish (NFE)

AF:

9.30e-7

AC:

AN:

1074964

Other (OTH)

AF:

0.00

AC:

AN:

56642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.8

PromoterAI

-0.071

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over