rs560397436

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000552.5(VWF):c.3414C>T(p.Asn1138Asn) 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 0.048 ( 207 hom., cov: 13)

Exomes 𝑓: 0.064 ( 1059 hom. )

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.04

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

hereditary von Willebrand disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
von Willebrand disease type 2B
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
von Willebrand disease 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
von Willebrand disease 1
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
von Willebrand disease type 2A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease type 2M
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
von Willebrand disease type 2N
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

VWF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-6022864-G-A is Benign according to our data. Variant chr12-6022864-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.3414C>T	p.Asn1138Asn	synonymous_variant	Exon 26 of 52	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 link	c.3414C>T	p.Asn1138Asn	synonymous_variant	Exon 26 of 52		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.3414C>T	p.Asn1138Asn	synonymous_variant	Exon 26 of 52	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5 link	n.421-28930C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

5511

AN:

114326

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00897

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.000461

Gnomad SAS

AF:

0.0397

Gnomad FIN

AF:

0.0608

Gnomad MID

AF:

0.0894

Gnomad NFE

AF:

0.0679

Gnomad OTH

AF:

0.0496

GnomAD2 exomes

AF:

0.0509

AC:

2758

AN:

54170

AF XY:

0.0521

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0496

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0992

Gnomad NFE exome

AF:

0.0774

Gnomad OTH exome

AF:

0.0696

GnomAD4 exome

AF:

0.0639

AC:

26989

AN:

422162

Hom.:

1059

Cov.:

AF XY:

0.0634

AC XY:

14170

AN XY:

223672

show subpopulations

African (AFR)

AF:

0.0139

AC:

164

AN:

11778

American (AMR)

AF:

0.0482

AC:

864

AN:

17938

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

1434

AN:

12712

East Asian (EAS)

AF:

0.000143

AC:

AN:

28040

South Asian (SAS)

AF:

0.0415

AC:

1873

AN:

45102

European-Finnish (FIN)

AF:

0.0725

AC:

1830

AN:

25254

Middle Eastern (MID)

AF:

0.0986

AC:

180

AN:

1826

European-Non Finnish (NFE)

AF:

0.0741

AC:

18914

AN:

255254

Other (OTH)

AF:

0.0712

AC:

1726

AN:

24258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1186

2373

3559

4746

5932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0481

AC:

5505

AN:

114432

Hom.:

207

Cov.:

AF XY:

0.0468

AC XY:

2484

AN XY:

53030

show subpopulations

African (AFR)

AF:

0.0106

AC:

310

AN:

29274

American (AMR)

AF:

0.0466

AC:

468

AN:

10044

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

316

AN:

2970

East Asian (EAS)

AF:

0.000463

AC:

AN:

4322

South Asian (SAS)

AF:

0.0401

AC:

113

AN:

2820

European-Finnish (FIN)

AF:

0.0608

AC:

384

AN:

6318

Middle Eastern (MID)

AF:

0.0857

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0679

AC:

3813

AN:

56194

Other (OTH)

AF:

0.0476

AC:

AN:

1430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

253

505

758

1010

1263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0891

Hom.:

Bravo

AF:

0.0491

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 28, 2022

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

von Willebrand disease type 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

von Willebrand disease type 3

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

von Willebrand disease type 1

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary von Willebrand disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.10

(source)

DANN

Benign

0.67

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over