Variant X-155220227-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003372.7(VBP1):c.138A>C(p.Ala46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,198,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 94 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 45 hem., cov: 23)

Exomes 𝑓: 0.00016 ( 0 hom. 49 hem. )

Consequence

VBP1
NM_003372.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.604

Variant links:

Genes affected

VBP1 (HGNC:12662): (VHL binding protein 1) The protein encoded by this gene interacts with the Von Hippel-Lindau protein to form an intracellular complex. The encoded protein functions as a chaperone protein, and may play a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. Alternative splicing and the use of alternate transcription start sites results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Jan 2015]

VBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-155220227-A-C is Benign according to our data. Variant chrX-155220227-A-C is described in ClinVar as [Benign]. Clinvar id is 781579.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.604 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 45 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VBP1	NM_003372.7 linkuse as main transcript	c.138A>C	p.Ala46=	synonymous_variant	2/6	ENST00000286428.7
VBP1	NM_001303543.1 linkuse as main transcript	c.246A>C	p.Ala82=	synonymous_variant	2/6
VBP1	NM_001303544.1 linkuse as main transcript	c.123A>C	p.Ala41=	synonymous_variant	3/7
VBP1	NM_001303545.1 linkuse as main transcript	c.27A>C	p.Ala9=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VBP1	ENST00000286428.7 linkuse as main transcript	c.138A>C	p.Ala46=	synonymous_variant	2/6	1	NM_003372.7	P1	P61758-1
VBP1	ENST00000535916.5 linkuse as main transcript	c.123A>C	p.Ala41=	synonymous_variant	3/7	2			P61758-2
VBP1	ENST00000625964.2 linkuse as main transcript	c.123A>C	p.Ala41=	synonymous_variant	2/6	5			P61758-2

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

175

AN:

111936

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

34104

show subpopulations

Gnomad AFR

AF:

0.00546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.000463

AC:

AN:

174896

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

60200

show subpopulations

Gnomad AFR exome

AF:

0.00588

Gnomad AMR exome

AF:

0.000193

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000464

GnomAD4 exome

AF:

0.000156

AC:

170

AN:

1086499

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

353383

show subpopulations

Gnomad4 AFR exome

AF:

0.00554

Gnomad4 AMR exome

AF:

0.000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000359

Gnomad4 OTH exome

AF:

0.000285

GnomAD4 genome

AF:

0.00156

AC:

175

AN:

111992

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

34170

show subpopulations

Gnomad4 AFR

AF:

0.00544

Gnomad4 AMR

AF:

0.000379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.00170

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.4

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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