Genetic Variant NM_000552.5:c.*204C>T (chr12-5948811-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000552.5(VWF):c.*204C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 632,192 control chromosomes in the GnomAD database, including 10,443 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 0.18 ( 2563 hom., cov: 33)

Exomes 𝑓: 0.17 ( 7880 hom. )

Consequence

VWF
NM_000552.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5 link	c.*204C>T		downstream_gene_variant		ENST00000261405.10	NP_000543.3	P04275-1
VWF	XM_047429501.1 link	c.*204C>T		downstream_gene_variant			XP_047285457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10 link	c.*204C>T		downstream_gene_variant		1	NM_000552.5	ENSP00000261405.5		P04275-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27003

AN:

152076

Hom.:

2557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.172

AC:

82764

AN:

479996

Hom.:

7880

AF XY:

0.178

AC XY:

45150

AN XY:

253402

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0233

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.178

AC:

27032

AN:

152196

Hom.:

2563

Cov.:

AF XY:

0.174

AC XY:

12944

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.0291

Gnomad4 SAS

AF:

0.247

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.117

Hom.:

270

Bravo

AF:

0.180

Asia WGS

AF:

0.136

AC:

478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.19

DANN

Benign

0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over