rs546732699

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000552.5(VWF):c.3486A>G(p.Pro1162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 525 hom., cov: 10)

Exomes 𝑓: 0.0082 ( 276 hom. )

Failed GnomAD Quality Control

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.66

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 12-6022792-T-C is Benign according to our data. Variant chr12-6022792-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 256670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6022792-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BS2

High AC in GnomAd at 4843 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5 linkuse as main transcript	c.3486A>G	p.Pro1162=	synonymous_variant	26/52	ENST00000261405.10
VWF	XM_047429501.1 linkuse as main transcript	c.3486A>G	p.Pro1162=	synonymous_variant	26/52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.3486A>G	p.Pro1162=	synonymous_variant	26/52	1	NM_000552.5	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.421-28858A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

4843

AN:

89306

Hom.:

523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0178

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000540

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0185

Gnomad NFE

AF:

0.000962

Gnomad OTH

AF:

0.0650

GnomAD3 exomes

AF:

0.0256

AC:

1391

AN:

54270

Hom.:

125

AF XY:

0.0228

AC XY:

624

AN XY:

27356

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00990

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00825

AC:

3624

AN:

439440

Hom.:

276

Cov.:

AF XY:

0.00702

AC XY:

1628

AN XY:

231798

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000489

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000897

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0543

AC:

4855

AN:

89346

Hom.:

525

Cov.:

AF XY:

0.0545

AC XY:

2159

AN XY:

39602

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000541

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000962

Gnomad4 OTH

AF:

0.0644

Alfa

AF:

0.0865

Hom.:

Bravo

AF:

0.0730

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

von Willebrand disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

von Willebrand disease type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

von Willebrand disease type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Hereditary von Willebrand disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

0.11

Dann

Benign

0.41

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