rs11063995

Positions:

• chr12-6026987-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.2968-941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,066 control chromosomes in the GnomAD database, including 6,821 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 0.28 (6821 hom., cov: 32)
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5	c.2968-941A>G		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.2968-941A>G		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.2968-941A>G		intron_variant		1	NM_000552.5	ENSP00000261405	P1
VWF	ENST00000538635.5	n.421-33053A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42851 AN: 151948 Hom.: 6808 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.282 AC: 42905 AN: 152066 Hom.: 6821 Cov.: 32 AF XY: 0.274 AC XY: 20399 AN XY: 74340

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.260

Alfa AF: 0.271 Hom.: 978

Bravo AF: 0.288

Asia WGS AF: 0.0860 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.74

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: rs11063995; hg19: chr12-6136153;