rs116243373

chr12-6022084-G-Achr12-6022084-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000552.5(VWF):c.3539-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,612,620 control chromosomes in the GnomAD database, including 1,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (1004 hom., cov: 31)
  • Exomes 𝑓: 0.0068 (880 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-6022084-G-A is Benign according to our data. Variant chr12-6022084-G-A is described in ClinVar as [Benign]. Clinvar id is 256672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWF	NM_000552.5	c.3539-49C>T		intron_variant		ENST00000261405.10
VWF	XM_047429501.1	c.3539-49C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWF	ENST00000261405.10	c.3539-49C>T		intron_variant		1	NM_000552.5	P1
VWF	ENST00000538635.5	n.421-28150C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9716 AN: 152034 Hom.: 1001 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0612

GnomAD3 exomes AF: 0.0169 AC: 4246 AN: 250952 Hom.: 392 AF XY: 0.0127 AC XY: 1719 AN XY: 135738

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00864

GnomAD4 exome AF: 0.00678 AC: 9902 AN: 1460468 Hom.: 880 Cov.: 31 AF XY: 0.00590 AC XY: 4288 AN XY: 726566

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0151

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000712

Gnomad4 OTH exome AF: 0.0150

GnomAD4 genome AF: 0.0640 AC: 9741 AN: 152152 Hom.: 1004 Cov.: 31 AF XY: 0.0616 AC XY: 4583 AN XY: 74384

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0373 Hom.: 142

Bravo AF: 0.0739

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.22
Dann	Benign	0.47

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: rs116243373; hg19: chr12-6131250;