rs3819540

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000552.5(VWF):c.7288-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,613,750 control chromosomes in the GnomAD database, including 7,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 697 hom., cov: 32)

Exomes 𝑓: 0.089 ( 6368 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.888

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-5976279-G-A is Benign according to our data. Variant chr12-5976279-G-A is described in ClinVar as Benign. ClinVar VariationId is 256697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.7288-19C>T		intron_variant	Intron 42 of 51	ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 link	c.7288-19C>T		intron_variant	Intron 42 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.7288-19C>T		intron_variant	Intron 42 of 51	1	NM_000552.5	ENSP00000261405.5		P04275-1

Frequencies

GnomAD3 genomes

AF:

0.0858

AC:

13048

AN:

152082

Hom.:

697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.0769

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.0803

GnomAD2 exomes

AF:

0.0950

AC:

23820

AN:

250804

AF XY:

0.0967

show subpopulations

Gnomad AFR exome

AF:

0.0608

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0767

Gnomad EAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.0965

Gnomad NFE exome

AF:

0.0812

Gnomad OTH exome

AF:

0.0849

GnomAD4 exome

AF:

0.0887

AC:

129645

AN:

1461550

Hom.:

6368

Cov.:

AF XY:

0.0897

AC XY:

65232

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.0631

AC:

2113

AN:

33476

American (AMR)

AF:

0.0580

AC:

2596

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

1996

AN:

26132

East Asian (EAS)

AF:

0.222

AC:

8825

AN:

39692

South Asian (SAS)

AF:

0.118

AC:

10159

AN:

86248

European-Finnish (FIN)

AF:

0.0958

AC:

5112

AN:

53356

Middle Eastern (MID)

AF:

0.0635

AC:

366

AN:

5762

European-Non Finnish (NFE)

AF:

0.0834

AC:

92769

AN:

1111780

Other (OTH)

AF:

0.0945

AC:

5709

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

6246

12492

18739

24985

31231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3554

7108

10662

14216

17770

<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:

0.0857

AC:

13051

AN:

152200

Hom.:

697

Cov.:

AF XY:

0.0871

AC XY:

6485

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0633

AC:

2628

AN:

41546

American (AMR)

AF:

0.0693

AC:

1060

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

267

AN:

3472

East Asian (EAS)

AF:

0.251

AC:

1298

AN:

5162

South Asian (SAS)

AF:

0.124

AC:

600

AN:

4820

European-Finnish (FIN)

AF:

0.105

AC:

1111

AN:

10592

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0851

AC:

5786

AN:

67994

Other (OTH)

AF:

0.0795

AC:

168

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

600

1199

1799

2398

2998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0650

Hom.:

210

Bravo

AF:

0.0816

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.026

(source)

DANN

Benign

0.62

PhyloP100

-0.89

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