ENST00000441350.2:c.1239T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The ENST00000441350.2(VPS13B):c.1239T>G(p.Tyr413*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,610,834 control chromosomes in the GnomAD database, including 490,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42338 hom., cov: 32)

Exomes 𝑓: 0.78 ( 448444 hom. )

Consequence

VPS13B
ENST00000441350.2 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.239

Publications

42 publications found

Variant links:

Genes affected

VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

VPS13B Gene-Disease associations (from GenCC):

Cohen syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00721 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 8-99121478-T-G is Benign according to our data. Variant chr8-99121478-T-G is described in ClinVar as [Benign]. Clinvar id is 262657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13B	NM_017890.5 link	c.1206+33T>G		intron_variant	Intron 8 of 61	ENST00000358544.7	NP_060360.3	Q7Z7G8-1
VPS13B	NM_152564.5 link	c.1206+33T>G		intron_variant	Intron 8 of 61	ENST00000357162.7	NP_689777.3	Q7Z7G8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7 link	c.1206+33T>G		intron_variant	Intron 8 of 61	1	NM_017890.5	ENSP00000351346.2		Q7Z7G8-1
VPS13B	ENST00000357162.7 link	c.1206+33T>G		intron_variant	Intron 8 of 61	1	NM_152564.5	ENSP00000349685.2		Q7Z7G8-2

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112575

AN:

151944

Hom.:

42332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.866

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.797

Gnomad OTH

AF:

0.735

GnomAD2 exomes

AF:

0.739

AC:

183487

AN:

248432

AF XY:

0.756

show subpopulations

Gnomad AFR exome

AF:

0.685

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.817

Gnomad EAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.780

Gnomad NFE exome

AF:

0.798

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.781

AC:

1139503

AN:

1458772

Hom.:

448444

Cov.:

AF XY:

0.785

AC XY:

569785

AN XY:

725430

show subpopulations

African (AFR)

AF:

0.682

AC:

22717

AN:

33290

American (AMR)

AF:

0.519

AC:

23032

AN:

44336

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

21305

AN:

26018

East Asian (EAS)

AF:

0.586

AC:

23231

AN:

39648

South Asian (SAS)

AF:

0.871

AC:

74858

AN:

85978

European-Finnish (FIN)

AF:

0.789

AC:

41873

AN:

53058

Middle Eastern (MID)

AF:

0.818

AC:

4699

AN:

5746

European-Non Finnish (NFE)

AF:

0.793

AC:

881050

AN:

1110442

Other (OTH)

AF:

0.776

AC:

46738

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

12992

25984

38975

51967

64959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.741

AC:

112622

AN:

152062

Hom.:

42338

Cov.:

AF XY:

0.738

AC XY:

54870

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.684

AC:

28358

AN:

41480

American (AMR)

AF:

0.608

AC:

9294

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2859

AN:

3470

East Asian (EAS)

AF:

0.569

AC:

2942

AN:

5166

South Asian (SAS)

AF:

0.866

AC:

4174

AN:

4818

European-Finnish (FIN)

AF:

0.785

AC:

8270

AN:

10540

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.797

AC:

54182

AN:

67988

Other (OTH)

AF:

0.738

AC:

1555

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1480

2960

4439

5919

7399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.778

Hom.:

100752

Bravo

AF:

0.718

TwinsUK

AF:

0.809

AC:

2999

ALSPAC

AF:

0.803

AC:

3095

ESP6500AA

AF:

0.681

AC:

3001

ESP6500EA

AF:

0.794

AC:

6827

ExAC

AF:

0.749

AC:

90921

Asia WGS

AF:

0.686

AC:

2384

AN:

3478

EpiCase

AF:

0.792

EpiControl

AF:

0.798

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cohen syndrome

Benign:4

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 02, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Sep 08, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

(source)

DANN

Benign

0.87

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.12

PhyloP100

0.24

Vest4

0.044

GERP RS

3.3

Mutation Taster

=189/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

ENST00000441350.2:c.1239T>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over