Variant rs57349683 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.5312-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,824 control chromosomes in the GnomAD database, including 2,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 1095 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 999 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.430

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:

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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=-0.97).

BP6

Variant 12-6016279-C-G is Benign according to our data. Variant chr12-6016279-C-G is described in ClinVar as [Benign]. Clinvar id is 256683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.5312-47G>C		intron_variant		ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 link	c.5312-47G>C		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.5312-47G>C		intron_variant		1	NM_000552.5	ENSP00000261405.5		P04275-1
VWF	ENST00000538635.5 link	n.421-22345G>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

10157

AN:

152082

Hom.:

1094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0356

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.0623

GnomAD3 exomes

AF:

0.0186

AC:

4662

AN:

251056

Hom.:

434

AF XY:

0.0138

AC XY:

1869

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000654

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00778

AC:

11373

AN:

1461624

Hom.:

999

Cov.:

AF XY:

0.00678

AC XY:

4928

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.00677

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000894

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00129

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0669

AC:

10188

AN:

152200

Hom.:

1095

Cov.:

AF XY:

0.0644

AC XY:

4796

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.0356

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.0617

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0771

Asia WGS

AF:

0.0180

AC:

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

-0.97

CADD

Benign

1.0

DANN

Benign

0.36

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