rs2239161

Variant names:

• chr12-6053495-G-A
• rs2239161
• NM_000552.5:c.1946-712C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6053495-G-A
• chr12-6053495-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.1946-712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,226 control chromosomes in the GnomAD database, including 61,656 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 0.90 (61656 hom., cov: 32)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.1946-712C>T		intron_variant	Intron 15 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.1946-712C>T		intron_variant	Intron 15 of 51		XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.1946-712C>T		intron_variant	Intron 15 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.420+57020C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136715 AN: 152106 Hom.: 61602 Cov.: 32

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.899 AC: 136827 AN: 152226 Hom.: 61656 Cov.: 32 AF XY: 0.898 AC XY: 66816 AN XY: 74404

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.913

Alfa AF: 0.886 Hom.: 13687

Bravo AF: 0.906

Asia WGS AF: 0.835 AC: 2905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.75

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: rs2239161; hg19: chr12-6162661;