Variant rs2270152 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 NM_000552.5(VWF):c.8116-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,612,966 control chromosomes in the GnomAD database, including 35,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.17 ( 2428 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32613 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.45

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

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-5951903-T-G is Benign according to our data. Variant chr12-5951903-T-G is described in ClinVar as [Benign]. Clinvar id is 256703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-5951903-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 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.8116-20A>C		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 linkuse as main transcript	c.8116-20A>C		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.8116-20A>C		intron_variant		1	NM_000552.5	ENSP00000261405	P1	P04275-1
VWF	ENST00000612016.1 linkuse as main transcript	n.525-20A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25972

AN:

152010

Hom.:

2431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0922

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.194

AC:

48786

AN:

251342

Hom.:

5108

AF XY:

0.201

AC XY:

27291

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0918

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.208

AC:

304456

AN:

1460838

Hom.:

32613

Cov.:

AF XY:

0.210

AC XY:

152314

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.0894

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.171

AC:

25981

AN:

152128

Hom.:

2428

Cov.:

AF XY:

0.169

AC XY:

12578

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0924

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.197

Hom.:

729

Bravo

AF:

0.169

Asia WGS

AF:

0.213

AC:

740

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.056

DANN

Benign

0.26

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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