rs73051263

Variant names:

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.3222+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,485,324 control chromosomes in the GnomAD database, including 42,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6822 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35204 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.05

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-6025549-G-A is Benign according to our data. Variant chr12-6025549-G-A is described in ClinVar as Benign. ClinVar VariationId is 256662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.3222+31C>T		intron_variant	Intron 24 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 link	c.3222+31C>T		intron_variant	Intron 24 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.3222+31C>T		intron_variant	Intron 24 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5 link	n.421-31615C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42827

AN:

151868

Hom.:

6809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.203

AC:

48777

AN:

240486

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.000440

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.218

GnomAD4 exome

AF:

0.223

AC:

297209

AN:

1333338

Hom.:

35204

Cov.:

AF XY:

0.220

AC XY:

146985

AN XY:

668846

show subpopulations

African (AFR)

AF:

0.418

AC:

12500

AN:

29918

American (AMR)

AF:

0.134

AC:

5841

AN:

43744

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

5995

AN:

25230

East Asian (EAS)

AF:

0.000305

AC:

AN:

39378

South Asian (SAS)

AF:

0.114

AC:

9476

AN:

83222

European-Finnish (FIN)

AF:

0.248

AC:

13086

AN:

52774

Middle Eastern (MID)

AF:

0.185

AC:

919

AN:

4960

European-Non Finnish (NFE)

AF:

0.237

AC:

236628

AN:

997872

Other (OTH)

AF:

0.227

AC:

12752

AN:

56240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

9647

19294

28940

38587

48234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7424

14848

22272

29696

37120

<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:

0.282

AC:

42881

AN:

151986

Hom.:

6822

Cov.:

AF XY:

0.274

AC XY:

20396

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.424

AC:

17540

AN:

41416

American (AMR)

AF:

0.208

AC:

3184

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

831

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5174

South Asian (SAS)

AF:

0.110

AC:

527

AN:

4802

European-Finnish (FIN)

AF:

0.249

AC:

2629

AN:

10574

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17338

AN:

67950

Other (OTH)

AF:

0.261

AC:

549

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1475

2950

4424

5899

7374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.268

Hom.:

1068

Bravo

AF:

0.288

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 11, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.89

CADD

Benign

0.046

(source)

DANN

Benign

0.52

PhyloP100

-4.1

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

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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