Variant rs55907031 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 ENST00000261405.10(VWF):c.998-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,570,608 control chromosomes in the GnomAD database, including 13,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2536 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10755 hom. )

Consequence

VWF
ENST00000261405.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0250

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=-0.83).

BP6

Variant 12-6072469-G-A is Benign according to our data. Variant chr12-6072469-G-A is described in ClinVar as [Benign]. Clinvar id is 256705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 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.998-27C>T		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1 linkuse as main transcript	c.998-27C>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.998-27C>T		intron_variant		1	NM_000552.5	ENSP00000261405	P1	P04275-1
VWF	ENST00000538635.5 linkuse as main transcript	n.420+38046C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24039

AN:

152012

Hom.:

2529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0839

Gnomad ASJ

AF:

0.0495

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.122

AC:

29991

AN:

246360

Hom.:

2270

AF XY:

0.123

AC XY:

16333

AN XY:

133214

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.0568

Gnomad ASJ exome

AF:

0.0569

Gnomad EAS exome

AF:

0.178

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.115

AC:

163641

AN:

1418476

Hom.:

10755

Cov.:

AF XY:

0.116

AC XY:

82469

AN XY:

708062

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.0602

Gnomad4 ASJ exome

AF:

0.0571

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.158

AC:

24072

AN:

152132

Hom.:

2536

Cov.:

AF XY:

0.157

AC XY:

11662

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.0836

Gnomad4 ASJ

AF:

0.0495

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.0943

Hom.:

265

Bravo

AF:

0.161

Asia WGS

AF:

0.177

AC:

615

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	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 28, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.83

CADD

Benign

0.55

DANN

Benign

0.62

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