Variant rs216325 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.2546+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,609,928 control chromosomes in the GnomAD database, including 365,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38221 hom., cov: 33)

Exomes 𝑓: 0.67 ( 327528 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.15

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=-0.92).

BP6

Variant 12-6036363-G-A is Benign according to our data. Variant chr12-6036363-G-A is described in ClinVar as [Benign]. Clinvar id is 256661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 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.2546+25C>T		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 linkuse as main transcript	c.2546+25C>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.2546+25C>T		intron_variant		1	NM_000552.5	ENSP00000261405	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.421-42429C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.706

AC:

107340

AN:

152014

Hom.:

38193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.762

Gnomad FIN

AF:

0.648

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.719

GnomAD3 exomes

AF:

0.706

AC:

176978

AN:

250800

Hom.:

63065

AF XY:

0.703

AC XY:

95279

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.771

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.792

Gnomad SAS exome

AF:

0.747

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.696

GnomAD4 exome

AF:

0.668

AC:

974067

AN:

1457796

Hom.:

327528

Cov.:

AF XY:

0.670

AC XY:

485977

AN XY:

725516

show subpopulations

Gnomad4 AFR exome

AF:

0.768

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.707

Gnomad4 EAS exome

AF:

0.794

Gnomad4 SAS exome

AF:

0.740

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.706

AC:

107417

AN:

152132

Hom.:

38221

Cov.:

AF XY:

0.711

AC XY:

52860

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.774

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.790

Gnomad4 SAS

AF:

0.762

Gnomad4 FIN

AF:

0.648

Gnomad4 NFE

AF:

0.654

Gnomad4 OTH

AF:

0.716

Alfa

AF:

0.671

Hom.:

34343

Bravo

AF:

0.716

Asia WGS

AF:

0.770

AC:

2676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 06, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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

-0.92

CADD

Benign

0.012

DANN

Benign

0.75

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