Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000397420.9(CD151):c.579G>A(p.Gly193Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,612,376 control chromosomes in the GnomAD database, including 379,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G193G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.65 ( 33089 hom., cov: 34)

Exomes 𝑓: 0.68 ( 346811 hom. )

Consequence

CD151
ENST00000397420.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0920

Publications

40 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 links:

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

POLR2L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-837582-G-A is Benign according to our data. Variant chr11-837582-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397420.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD151	NM_004357.5	MANE Select	c.579G>A	p.Gly193Gly	synonymous	Exon 7 of 9	NP_004348.2
CD151	NM_001039490.2		c.579G>A	p.Gly193Gly	synonymous	Exon 6 of 8	NP_001034579.1
CD151	NM_139029.2		c.579G>A	p.Gly193Gly	synonymous	Exon 7 of 9	NP_620598.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD151	ENST00000397420.9	TSL:1 MANE Select	c.579G>A	p.Gly193Gly	synonymous	Exon 7 of 9	ENSP00000380565.3
CD151	ENST00000322008.9	TSL:1	c.579G>A	p.Gly193Gly	synonymous	Exon 7 of 9	ENSP00000324101.4
CD151	ENST00000397421.5	TSL:1	c.579G>A	p.Gly193Gly	synonymous	Exon 6 of 8	ENSP00000380566.1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99089

AN:

151874

Hom.:

33077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.736

Gnomad AMR

AF:

0.726

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.873

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.693

Gnomad OTH

AF:

0.623

GnomAD2 exomes

AF:

0.681

AC:

170009

AN:

249696

AF XY:

0.666

show subpopulations

Gnomad AFR exome

AF:

0.541

Gnomad AMR exome

AF:

0.819

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.861

Gnomad FIN exome

AF:

0.757

Gnomad NFE exome

AF:

0.686

Gnomad OTH exome

AF:

0.667

GnomAD4 exome

AF:

0.684

AC:

999333

AN:

1460384

Hom.:

346811

Cov.:

AF XY:

0.677

AC XY:

491826

AN XY:

726500

show subpopulations

African (AFR)

AF:

0.525

AC:

17565

AN:

33470

American (AMR)

AF:

0.811

AC:

36246

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

12812

AN:

26136

East Asian (EAS)

AF:

0.888

AC:

35238

AN:

39698

South Asian (SAS)

AF:

0.484

AC:

41728

AN:

86240

European-Finnish (FIN)

AF:

0.752

AC:

39409

AN:

52406

Middle Eastern (MID)

AF:

0.512

AC:

2940

AN:

5738

European-Non Finnish (NFE)

AF:

0.696

AC:

773874

AN:

1111648

Other (OTH)

AF:

0.655

AC:

39521

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16569

33138

49707

66276

82845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19570

39140

58710

78280

97850

<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:

0.652

AC:

99129

AN:

151992

Hom.:

33089

Cov.:

AF XY:

0.652

AC XY:

48462

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.540

AC:

22394

AN:

41452

American (AMR)

AF:

0.726

AC:

11094

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1679

AN:

3468

East Asian (EAS)

AF:

0.873

AC:

4487

AN:

5140

South Asian (SAS)

AF:

0.482

AC:

2318

AN:

4808

European-Finnish (FIN)

AF:

0.750

AC:

7930

AN:

10572

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47086

AN:

67958

Other (OTH)

AF:

0.625

AC:

1319

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.661

Hom.:

64971

Bravo

AF:

0.651

Asia WGS

AF:

0.682

AC:

2370

AN:

3478

EpiCase

AF:

0.663

EpiControl

AF:

0.665

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

(source)

DANN

Benign

0.83

PhyloP100

-0.092

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over