dbSNP rs766578698: CD81:p.Cys9Cys (chr11-2377576-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_004356.4(CD81):c.27C>T(p.Cys9Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000654 in 1,529,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CD81
NM_004356.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.848

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 11-2377576-C-T is Benign according to our data. Variant chr11-2377576-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2186773.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.848 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.27C>T	p.Cys9Cys	synonymous	Exon 1 of 8	NP_004347.1	P60033
CD81	NM_001425135.1		c.27C>T	p.Cys9Cys	synonymous	Exon 1 of 8	NP_001412064.1
CD81	NM_001425137.1		c.27C>T	p.Cys9Cys	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.27C>T	p.Cys9Cys	synonymous	Exon 1 of 8	ENSP00000263645.5	P60033
CD81-AS1	ENST00000427151.1	TSL:1	n.404+10G>A		intron	N/A
CD81	ENST00000905044.1		c.27C>T	p.Cys9Cys	synonymous	Exon 4 of 11	ENSP00000575103.1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000210

AC:

AN:

190272

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000653

AC:

AN:

1378232

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

683674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28686

American (AMR)

AF:

0.00

AC:

AN:

37616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23542

East Asian (EAS)

AF:

0.000183

AC:

AN:

32770

South Asian (SAS)

AF:

0.00

AC:

AN:

79436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5192

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1067116

Other (OTH)

AF:

0.0000180

AC:

AN:

55666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.564

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

AF:

0.00000663

AC:

AN:

150770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41234

American (AMR)

AF:

0.00

AC:

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.000196

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67630

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

0.85

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over