rs55664929

Variant names:

• chr12-6012054-C-T
• rs55664929
• NM_000552.5:c.5664+33G>A

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.5664+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00986 in 1,610,032 control chromosomes in the GnomAD database, including 1,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (720 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (494 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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=-0.91).
• BP6: Variant 12-6012054-C-T is Benign according to our data. Variant chr12-6012054-C-T is described in ClinVar as [Benign]. Clinvar id is 256686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6012054-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.5664+33G>A		intron_variant	Intron 33 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.5664+33G>A		intron_variant	Intron 33 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.5664+33G>A		intron_variant	Intron 33 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.421-18120G>A		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8469 AN: 152118 Hom.: 721 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.00690 AC: 1715 AN: 248640 AF XY: 0.00534

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00505

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00507 AC: 7391 AN: 1457798 Hom.: 494 Cov.: 31 AF XY: 0.00439 AC XY: 3187 AN XY: 725522

Gnomad4 AFR exome AF: 0.164 AC: 5138 AN: 31278

Gnomad4 AMR exome AF: 0.0113 AC: 505 AN: 44598

Gnomad4 ASJ exome AF: 0.00606 AC: 158 AN: 26086

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39694

Gnomad4 SAS exome AF: 0.000615 AC: 53 AN: 86228

Gnomad4 FIN exome AF: 0.0000187 AC: 1 AN: 53420

Gnomad4 NFE exome AF: 0.000694 AC: 771 AN: 1110600

Gnomad4 Remaining exome AF: 0.0114 AC: 687 AN: 60146

GnomAD4 genome AF: 0.0558 AC: 8488 AN: 152234 Hom.: 720 Cov.: 32 AF XY: 0.0533 AC XY: 3971 AN XY: 74452

Gnomad4 AFR AF: 0.189 AC: 0.188603 AN: 0.188603

Gnomad4 AMR AF: 0.0282 AC: 0.028239 AN: 0.028239

Gnomad4 ASJ AF: 0.00806 AC: 0.00806452 AN: 0.00806452

Gnomad4 EAS AF: 0.000193 AC: 0.000192827 AN: 0.000192827

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00140 AC: 0.00139636 AN: 0.00139636

Gnomad4 OTH AF: 0.0516 AC: 0.051561 AN: 0.051561

Alfa AF: 0.0307 Hom.: 72

Bravo AF: 0.0643

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.27
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: rs55664929; hg19: chr12-6121220;