12-6013431-A-T

Position:

• chr12-6013431-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000552.5(VWF):​c.5620+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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]

VWF (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWF	NM_000552.5	c.5620+50T>A		intron_variant		ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.5620+50T>A		intron_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.5620+50T>A		intron_variant		1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000538635.5	n.421-19497T>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152010 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000975 AC: 237 AN: 243116 Hom.: 0 AF XY: 0.000777 AC XY: 103 AN XY: 132480

Gnomad AFR exome AF: 0.000404

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00223

Gnomad EAS exome AF: 0.000220

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.0000957

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.000499

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000249 AC: 362 AN: 1455896 Hom.: 0 Cov.: 31 AF XY: 0.000294 AC XY: 213 AN XY: 724312

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000679

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.000191

Gnomad4 NFE exome AF: 0.000266

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.50

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: rs201000688; hg19: chr12-6122597;