rs10849378

Variant summary

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

The ENST00000261405.10(VWF):​c.2443-3017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,144 control chromosomes in the GnomAD database, including 4,802 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 0.24 ( 4802 hom., cov: 32)

Consequence

VWF
ENST00000261405.10 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VWFNM_000552.5 linkuse as main transcriptc.2443-3017C>T intron_variant ENST00000261405.10 NP_000543.3
VWFXM_047429501.1 linkuse as main transcriptc.2443-3017C>T intron_variant XP_047285457.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VWFENST00000261405.10 linkuse as main transcriptc.2443-3017C>T intron_variant 1 NM_000552.5 ENSP00000261405 P1P04275-1
VWFENST00000538635.5 linkuse as main transcriptn.421-45574C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.245
AC:
37193
AN:
152026
Hom.:
4792
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.223
Gnomad AMI
AF:
0.318
Gnomad AMR
AF:
0.208
Gnomad ASJ
AF:
0.264
Gnomad EAS
AF:
0.00231
Gnomad SAS
AF:
0.135
Gnomad FIN
AF:
0.267
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.287
Gnomad OTH
AF:
0.247
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.245
AC:
37235
AN:
152144
Hom.:
4802
Cov.:
32
AF XY:
0.238
AC XY:
17665
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.224
Gnomad4 AMR
AF:
0.207
Gnomad4 ASJ
AF:
0.264
Gnomad4 EAS
AF:
0.00232
Gnomad4 SAS
AF:
0.136
Gnomad4 FIN
AF:
0.267
Gnomad4 NFE
AF:
0.287
Gnomad4 OTH
AF:
0.244
Alfa
AF:
0.217
Hom.:
883
Bravo
AF:
0.242
Asia WGS
AF:
0.0830
AC:
293
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.013
DANN
Benign
0.71

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

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

Other links and lift over

dbSNP: rs10849378; hg19: chr12-6148674; API