Variant rs72676269 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152564.5(VPS13B):c.11044+33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,595,412 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 131 hom. )

Consequence

VPS13B
NM_152564.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.05

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 links:

VPS13B (HGNC:):

VPS13B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

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

BP6

Variant 8-99859513-C-A is Benign according to our data. Variant chr8-99859513-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 262654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-99859513-C-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13B	NM_017890.5 linkuse as main transcript	c.11119+33C>A		intron_variant		ENST00000358544.7	NP_060360.3	Q7Z7G8-1
VPS13B	NM_152564.5 linkuse as main transcript	c.11044+33C>A		intron_variant		ENST00000357162.7	NP_689777.3	Q7Z7G8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13B	ENST00000358544.7 linkuse as main transcript	c.11119+33C>A		intron_variant		1	NM_017890.5	ENSP00000351346.2		Q7Z7G8-1
VPS13B	ENST00000357162.7 linkuse as main transcript	c.11044+33C>A		intron_variant		1	NM_152564.5	ENSP00000349685.2		Q7Z7G8-2

Frequencies

GnomAD3 genomes

AF:

0.00789

AC:

1186

AN:

150296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00418

Gnomad ASJ

AF:

0.00232

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00168

Gnomad FIN

AF:

0.0150

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00724

GnomAD3 exomes

AF:

0.00877

AC:

2016

AN:

229860

Hom.:

AF XY:

0.00878

AC XY:

1105

AN XY:

125836

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.00377

Gnomad ASJ exome

AF:

0.00290

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00234

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00646

GnomAD4 exome

AF:

0.0118

AC:

17101

AN:

1445004

Hom.:

131

Cov.:

AF XY:

0.0116

AC XY:

8325

AN XY:

719376

show subpopulations

Gnomad4 AFR exome

AF:

0.00253

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00289

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.00852

GnomAD4 genome

AF:

0.00788

AC:

1185

AN:

150408

Hom.:

Cov.:

AF XY:

0.00771

AC XY:

566

AN XY:

73394

show subpopulations

Gnomad4 AFR

AF:

0.00276

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00232

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00168

Gnomad4 FIN

AF:

0.0150

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00716

Alfa

AF:

0.00840

Hom.:

Bravo

AF:

0.00656

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.050

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over