chr12-6019629-C-T

Position:

chr12-6019629-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting

The NM_000552.5(VWF):c.3789G>A(p.Ser1263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,611,968 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -7.15

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-6019629-C-T is Benign according to our data. Variant chr12-6019629-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 256674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6019629-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-7.15 with no splicing effect.

BS2

High AC in GnomAd4 at 255 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.3789G>A	p.Ser1263=	synonymous_variant	28/52	ENST00000261405.10
VWF	XM_047429501.1 linkuse as main transcript	c.3789G>A	p.Ser1263=	synonymous_variant	28/52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.3789G>A	p.Ser1263=	synonymous_variant	28/52	1	NM_000552.5	P1	P04275-1
VWF	ENST00000539641.1 linkuse as main transcript	n.587G>A		non_coding_transcript_exon_variant	3/3	3
VWF	ENST00000538635.5 linkuse as main transcript	n.421-25695G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00644

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00168

AC:

420

AN:

249542

Hom.:

AF XY:

0.00165

AC XY:

223

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00506

Gnomad SAS exome

AF:

0.00210

Gnomad FIN exome

AF:

0.00352

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00137

AC:

2001

AN:

1459764

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1081

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00884

Gnomad4 EAS exome

AF:

0.00376

Gnomad4 SAS exome

AF:

0.00453

Gnomad4 FIN exome

AF:

0.00453

Gnomad4 NFE exome

AF:

0.000728

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00168

AC:

255

AN:

152204

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00645

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00159

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	VWF: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Jun 17, 2022	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 14, 2020	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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

- -

von Willebrand disease type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0030

DANN

Benign

0.42

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