Genetic Variant CD151:c.-7-20C>T (chr11-836043-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004357.5(CD151):c.-7-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,507,524 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 15 hom., cov: 34)

Exomes 𝑓: 0.015 ( 191 hom. )

Consequence

CD151
NM_004357.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.147

Publications

0 publications found

Variant links:

Genes affected

CD151 (HGNC:1630): (CD151 molecule (Raph blood group)) 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 and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

CD151 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex 7, with nephropathy and deafness
Inheritance: AR, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet

CD151 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-836043-C-T is Benign according to our data. Variant chr11-836043-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1223149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0107 (1633/152328) while in subpopulation NFE AF = 0.016 (1091/68028). AF 95% confidence interval is 0.0152. There are 15 homozygotes in GnomAd4. There are 776 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004357.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD151	NM_004357.5	MANE Select	c.-7-20C>T	intron	N/A	NP_004348.2
CD151	NM_001039490.2		c.-7-20C>T	intron	N/A	NP_001034579.1	P48509
CD151	NM_139029.2		c.-7-20C>T	intron	N/A	NP_620598.1	P48509

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD151	ENST00000397420.9	TSL:1 MANE Select	c.-7-20C>T	intron	N/A	ENSP00000380565.3	P48509
CD151	ENST00000322008.9	TSL:1	c.-7-20C>T	intron	N/A	ENSP00000324101.4	P48509
CD151	ENST00000397421.5	TSL:1	c.-7-20C>T	intron	N/A	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1634

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.0111

AC:

2737

AN:

246812

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.00267

Gnomad AMR exome

AF:

0.00872

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0151

AC:

20518

AN:

1355196

Hom.:

191

Cov.:

AF XY:

0.0146

AC XY:

9895

AN XY:

679864

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

31394

American (AMR)

AF:

0.00883

AC:

392

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

320

AN:

25434

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39208

South Asian (SAS)

AF:

0.00362

AC:

304

AN:

83880

European-Finnish (FIN)

AF:

0.0193

AC:

1005

AN:

52036

Middle Eastern (MID)

AF:

0.00682

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.0173

AC:

17608

AN:

1016442

Other (OTH)

AF:

0.0137

AC:

778

AN:

56850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1022

2044

3067

4089

5111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.0107

AC:

1633

AN:

152328

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41564

American (AMR)

AF:

0.0101

AC:

155

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00249

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0210

AC:

223

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0160

AC:

1091

AN:

68028

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00806

Hom.:

Bravo

AF:

0.00996

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Epidermolysis bullosa simplex 7, with nephropathy and deafness;C1867341:RAPH BLOOD GROUP SYSTEM (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.4

(source)

DANN

Benign

0.89

PhyloP100

-0.15

PromoterAI

0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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