rs1800379

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000552.5(VWF):c.1548T>C(p.Tyr516Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,612,916 control chromosomes in the GnomAD database, including 111,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14101 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97445 hom. )

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:10

Conservation

PhyloP100: 0.193

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:

VWF (HGNC:):

VWF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-6058030-A-G is Benign according to our data. Variant chr12-6058030-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 256655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6058030-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5 linkuse as main transcript	c.1548T>C	p.Tyr516Tyr	synonymous_variant	14/52	ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 linkuse as main transcript	c.1548T>C	p.Tyr516Tyr	synonymous_variant	14/52		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.1548T>C	p.Tyr516Tyr	synonymous_variant	14/52	1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.420+52485T>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62259

AN:

152026

Hom.:

14071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.396

GnomAD3 exomes

AF:

0.334

AC:

82849

AN:

248268

Hom.:

15354

AF XY:

0.335

AC XY:

45232

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.608

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.366

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.359

AC:

524289

AN:

1460772

Hom.:

97445

Cov.:

AF XY:

0.357

AC XY:

259598

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.613

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.368

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.410

AC:

62330

AN:

152144

Hom.:

14101

Cov.:

AF XY:

0.402

AC XY:

29918

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.598

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.392

Alfa

AF:

0.363

Hom.:

16914

Bravo

AF:

0.410

Asia WGS

AF:

0.293

AC:

1023

AN:

3478

EpiCase

AF:

0.355

EpiControl

AF:

0.363

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	Allele frequency is common in at least one population database (frequency: 60.792% in gnomAD_Exomes) based on the frequency threshold of 0.5% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. A synonymous variant not located in a splice region. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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

- -

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

-0.88

CADD

Benign

0.74

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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