Variant chr12-6044493-G-T 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.2282-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,601,648 control chromosomes in the GnomAD database, including 240,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20148 hom., cov: 32)

Exomes 𝑓: 0.55 ( 220604 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.420

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:

VWF (HGNC:):

VWF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-6044493-G-T is Benign according to our data. Variant chr12-6044493-G-T is described in ClinVar as [Benign]. Clinvar id is 256658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 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.2282-42C>A		intron_variant		ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 linkuse as main transcript	c.2282-42C>A		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.2282-42C>A		intron_variant		1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.421-50559C>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74953

AN:

151954

Hom.:

20135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.585

AC:

135035

AN:

230794

Hom.:

40715

AF XY:

0.586

AC XY:

73229

AN XY:

124928

show subpopulations

Gnomad AFR exome

AF:

0.278

Gnomad AMR exome

AF:

0.740

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.722

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.590

GnomAD4 exome

AF:

0.547

AC:

793387

AN:

1449576

Hom.:

220604

Cov.:

AF XY:

0.550

AC XY:

396376

AN XY:

720474

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.723

Gnomad4 ASJ exome

AF:

0.649

Gnomad4 EAS exome

AF:

0.699

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.525

Gnomad4 NFE exome

AF:

0.535

Gnomad4 OTH exome

AF:

0.550

GnomAD4 genome

AF:

0.493

AC:

74994

AN:

152072

Hom.:

20148

Cov.:

AF XY:

0.501

AC XY:

37251

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.646

Gnomad4 ASJ

AF:

0.643

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.654

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.525

Hom.:

16024

Bravo

AF:

0.491

Asia WGS

AF:

0.640

AC:

2226

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

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

-0.84

CADD

Benign

1.9

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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