rs55907031

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.998-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,570,608 control chromosomes in the GnomAD database, including 13,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2536 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10755 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0250

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=-0.83).

BP6

Variant 12-6072469-G-A is Benign according to our data. Variant chr12-6072469-G-A is described in ClinVar as Benign. ClinVar VariationId is 256705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.998-27C>T		intron_variant	Intron 8 of 51	ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 link	c.998-27C>T		intron_variant	Intron 8 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.998-27C>T		intron_variant	Intron 8 of 51	1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 link	n.420+38046C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24039

AN:

152012

Hom.:

2529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0839

Gnomad ASJ

AF:

0.0495

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.122

AC:

29991

AN:

246360

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.0568

Gnomad ASJ exome

AF:

0.0569

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.115

AC:

163641

AN:

1418476

Hom.:

10755

Cov.:

AF XY:

0.116

AC XY:

82469

AN XY:

708062

show subpopulations

African (AFR)

AF:

0.295

AC:

9637

AN:

32654

American (AMR)

AF:

0.0602

AC:

2683

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

1473

AN:

25780

East Asian (EAS)

AF:

0.169

AC:

6671

AN:

39472

South Asian (SAS)

AF:

0.167

AC:

14217

AN:

85198

European-Finnish (FIN)

AF:

0.108

AC:

5714

AN:

53016

Middle Eastern (MID)

AF:

0.119

AC:

674

AN:

5686

European-Non Finnish (NFE)

AF:

0.107

AC:

115140

AN:

1073132

Other (OTH)

AF:

0.126

AC:

7432

AN:

58986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7255

14509

21764

29018

36273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4324

8648

12972

17296

21620

<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:

0.158

AC:

24072

AN:

152132

Hom.:

2536

Cov.:

AF XY:

0.157

AC XY:

11662

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.297

AC:

12317

AN:

41462

American (AMR)

AF:

0.0836

AC:

1279

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0495

AC:

172

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

911

AN:

5170

South Asian (SAS)

AF:

0.168

AC:

813

AN:

4828

European-Finnish (FIN)

AF:

0.109

AC:

1152

AN:

10590

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7076

AN:

67994

Other (OTH)

AF:

0.128

AC:

271

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

969

1939

2908

3878

4847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.110

Hom.:

519

Bravo

AF:

0.161

Asia WGS

AF:

0.177

AC:

615

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

Mar 28, 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

-0.83

CADD

Benign

0.55

(source)

DANN

Benign

0.62

PhyloP100

0.025

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