rs201000688

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.5620+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,607,146 control chromosomes in the GnomAD database, including 1,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 729 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 579 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.220

Publications

0 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 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
von Willebrand disease type 2B
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
von Willebrand disease 1
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
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=-0.9).

BP6

Variant 12-6013431-A-G is Benign according to our data. Variant chr12-6013431-A-G is described in ClinVar as Benign. ClinVar VariationId is 256685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000552.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWF	NM_000552.5	MANE Select	c.5620+50T>C		intron	N/A	NP_000543.3	P04275-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VWF	ENST00000261405.10	TSL:1 MANE Select	c.5620+50T>C	intron	N/A	ENSP00000261405.5	P04275-1
VWF	ENST00000895679.1		c.5620+50T>C	intron	N/A	ENSP00000565738.1
VWF	ENST00000895680.1		c.2967+15911T>C	intron	N/A	ENSP00000565739.1

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8501

AN:

151994

Hom.:

731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.0527

GnomAD2 exomes

AF:

0.0144

AC:

3505

AN:

243116

AF XY:

0.0110

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.00680

Gnomad EAS exome

AF:

0.0000551

Gnomad FIN exome

AF:

0.0000479

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00548

AC:

7979

AN:

1455034

Hom.:

579

Cov.:

AF XY:

0.00475

AC XY:

3437

AN XY:

723956

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.175

AC:

5602

AN:

31962

American (AMR)

AF:

0.0121

AC:

535

AN:

44160

Ashkenazi Jewish (ASJ)

AF:

0.00624

AC:

162

AN:

25942

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.000663

AC:

AN:

85958

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52496

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000723

AC:

802

AN:

1109152

Other (OTH)

AF:

0.0123

AC:

740

AN:

60132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.397

Heterozygous variant carriers

235

470

706

941

1176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.0560

AC:

8520

AN:

152112

Hom.:

729

Cov.:

AF XY:

0.0536

AC XY:

3988

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.189

AC:

7853

AN:

41484

American (AMR)

AF:

0.0283

AC:

432

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

67950

Other (OTH)

AF:

0.0521

AC:

110

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

348

697

1045

1394

1742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0318

Hom.:

Bravo

AF:

0.0643

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.45

PhyloP100

-0.22

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over