12-5975025-G-C

Position:

• chr12-5975025-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000552.5(VWF):​c.7437+1086C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,132 control chromosomes in the GnomAD database, including 27,874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27874 hom., cov: 33)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5	c.7437+1086C>G		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.7437+1086C>G		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.7437+1086C>G		intron_variant		1	NM_000552.5	ENSP00000261405.5

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89620 AN: 152014 Hom.: 27848 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.590 AC: 89698 AN: 152132 Hom.: 27874 Cov.: 33 AF XY: 0.596 AC XY: 44301 AN XY: 74366

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.619

Alfa AF: 0.520 Hom.: 1611

Bravo AF: 0.584

Asia WGS AF: 0.641 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.42

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: rs216852; hg19: chr12-6084191;