Variant chr12-6057952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000552.5(VWF):c.1626G>A(p.Ala542Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,613,666 control chromosomes in the GnomAD database, including 6,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 437 hom., cov: 31)

Exomes 𝑓: 0.090 ( 6488 hom. )

Consequence

VWF
NM_000552.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0730

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-6057952-C-T is Benign according to our data. Variant chr12-6057952-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 256656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6057952-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 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.1626G>A	p.Ala542Ala	synonymous_variant	14/52	ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 linkuse as main transcript	c.1626G>A	p.Ala542Ala	synonymous_variant	14/52		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 linkuse as main transcript	c.1626G>A	p.Ala542Ala	synonymous_variant	14/52	1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.420+52563G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0703

AC:

10696

AN:

152136

Hom.:

440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0422

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.0959

Gnomad FIN

AF:

0.0680

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.0642

GnomAD3 exomes

AF:

0.0792

AC:

19825

AN:

250416

Hom.:

944

AF XY:

0.0816

AC XY:

11072

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0422

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.0279

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.0908

Gnomad FIN exome

AF:

0.0768

Gnomad NFE exome

AF:

0.0907

Gnomad OTH exome

AF:

0.0738

GnomAD4 exome

AF:

0.0905

AC:

132254

AN:

1461412

Hom.:

6488

Cov.:

AF XY:

0.0904

AC XY:

65708

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.0308

Gnomad4 ASJ exome

AF:

0.0272

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0900

Gnomad4 FIN exome

AF:

0.0757

Gnomad4 NFE exome

AF:

0.0952

Gnomad4 OTH exome

AF:

0.0879

GnomAD4 genome

AF:

0.0702

AC:

10693

AN:

152254

Hom.:

437

Cov.:

AF XY:

0.0689

AC XY:

5131

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0436

Gnomad4 AMR

AF:

0.0421

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.0959

Gnomad4 FIN

AF:

0.0680

Gnomad4 NFE

AF:

0.0882

Gnomad4 OTH

AF:

0.0640

Alfa

AF:

0.0779

Hom.:

216

Bravo

AF:

0.0676

Asia WGS

AF:

0.118

AC:

411

AN:

3478

EpiCase

AF:

0.0816

EpiControl

AF:

0.0831

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 20, 2021	- -

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

- -

Hereditary von Willebrand disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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