Variant rs73051263 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000261405.10(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
ENST00000261405.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.05

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
VWF	NM_000552.5 linkuse as main transcript	c.3222+31C>T		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 linkuse as main transcript	c.3222+31C>T		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.3222+31C>T		intron_variant		1	NM_000552.5	ENSP00000261405	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.421-31615C>T		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.203

AC:

48777

AN:

240486

Hom.:

5939

AF XY:

0.197

AC XY:

25603

AN XY:

129640

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 SAS exome

AF:

0.113

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

Gnomad4 AFR exome

AF:

0.418

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.000305

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.248

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.282

AC:

42881

AN:

151986

Hom.:

6822

Cov.:

AF XY:

0.274

AC XY:

20396

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.261

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 11, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

von Willebrand disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

von Willebrand disease type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

von Willebrand disease type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.046

DANN

Benign

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over