rs377198574
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting
The NM_000552.5(VWF):c.1515C>T(p.Arg505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,612,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
VWF
NM_000552.5 synonymous
NM_000552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.969
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 12-6062972-G-A is Benign according to our data. Variant chr12-6062972-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 619929.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.969 with no splicing effect.
BS2
?
High AC in GnomAd4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.1515C>T | p.Arg505= | synonymous_variant | 13/52 | ENST00000261405.10 | |
VWF | XM_047429501.1 | c.1515C>T | p.Arg505= | synonymous_variant | 13/52 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.1515C>T | p.Arg505= | synonymous_variant | 13/52 | 1 | NM_000552.5 | P1 | |
VWF | ENST00000538635.5 | n.420+47543C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249208Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135082
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GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460636Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 726700
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 04, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at