chr12-5986108-T-C

Position:

• chr12-5986108-T-C

Variant summary

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

The NM_000552.5(VWF):​c.6799-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,052 control chromosomes in the GnomAD database, including 43,362 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 0.75 (43362 hom., cov: 31)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5	c.6799-443A>G		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.6799-443A>G		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.6799-443A>G		intron_variant		1	NM_000552.5	ENSP00000261405.5

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114213 AN: 151936 Hom.: 43319 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.752 AC: 114308 AN: 152052 Hom.: 43362 Cov.: 31 AF XY: 0.751 AC XY: 55795 AN XY: 74318

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.801

Gnomad4 OTH AF: 0.770

Alfa AF: 0.798 Hom.: 75670

Bravo AF: 0.752

Asia WGS AF: 0.699 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.61

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: rs216873; hg19: chr12-6095274;