Variant chr12-6034787-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_Very_StrongBP7BS2_Supporting

The NM_000552.5(VWF):c.2586G>T(p.Val862=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,248 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0410

Variant links:

Genes affected

VWF (HGNC:12726): (von Willebrand factor) This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]

VWF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-6034787-C-A is Benign according to our data. Variant chr12-6034787-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 439329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.041 with no splicing effect.

BS2

High AC in GnomAd4 at 190 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5 linkuse as main transcript	c.2586G>T	p.Val862=	synonymous_variant	20/52	ENST00000261405.10
VWF	XM_047429501.1 linkuse as main transcript	c.2586G>T	p.Val862=	synonymous_variant	20/52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.2586G>T	p.Val862=	synonymous_variant	20/52	1	NM_000552.5	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.421-40853G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

187

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000896

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00236

AC:

594

AN:

251486

Hom.:

AF XY:

0.00286

AC XY:

389

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00133

AC:

1940

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1176

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00655

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152358

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00101

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	VWF: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Feb 06, 2023	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 22, 2020

- -

VWF-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 06, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

1.5

DANN

Benign

0.68

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