rs55907031

Variant names:

• chr12-6072469-G-A
• rs55907031
• NM_000552.5:c.998-27C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6072469-G-A
• chr12-6072469-G-C
• chr12-6072469-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000552.5(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 NM_000552.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.998-27C>T		intron_variant	Intron 8 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.998-27C>T		intron_variant	Intron 8 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.998-27C>T		intron_variant	Intron 8 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.420+38046C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24039 AN: 152012 Hom.: 2529 Cov.: 32

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

GnomAD2 exomes AF: 0.122 AC: 29991 AN: 246360 AF XY: 0.123

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 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.: 25 AF XY: 0.116 AC XY: 82469 AN XY: 708062

Gnomad4 AFR exome AF: 0.295 AC: 9637 AN: 32654

Gnomad4 AMR exome AF: 0.0602 AC: 2683 AN: 44552

Gnomad4 ASJ exome AF: 0.0571 AC: 1473 AN: 25780

Gnomad4 EAS exome AF: 0.169 AC: 6671 AN: 39472

Gnomad4 SAS exome AF: 0.167 AC: 14217 AN: 85198

Gnomad4 FIN exome AF: 0.108 AC: 5714 AN: 53016

Gnomad4 NFE exome AF: 0.107 AC: 115140 AN: 1073132

Gnomad4 Remaining exome AF: 0.126 AC: 7432 AN: 58986

GnomAD4 genome AF: 0.158 AC: 24072 AN: 152132 Hom.: 2536 Cov.: 32 AF XY: 0.157 AC XY: 11662 AN XY: 74354

Gnomad4 AFR AF: 0.297 AC: 0.297067 AN: 0.297067

Gnomad4 AMR AF: 0.0836 AC: 0.0836057 AN: 0.0836057

Gnomad4 ASJ AF: 0.0495 AC: 0.0495392 AN: 0.0495392

Gnomad4 EAS AF: 0.176 AC: 0.176209 AN: 0.176209

Gnomad4 SAS AF: 0.168 AC: 0.168393 AN: 0.168393

Gnomad4 FIN AF: 0.109 AC: 0.108782 AN: 0.108782

Gnomad4 NFE AF: 0.104 AC: 0.104068 AN: 0.104068

Gnomad4 OTH AF: 0.128 AC: 0.128314 AN: 0.128314

Alfa AF: 0.110 Hom.: 519

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 28, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

von Willebrand disease type 2 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

von Willebrand disease type 3 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

von Willebrand disease type 1 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55907031; hg19: chr12-6181635; COSMIC: COSV107218080;