rs7980045
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000552.5(VWF):c.657+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,613,852 control chromosomes in the GnomAD database, including 3,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 1623 hom., cov: 31)
Exomes 𝑓: 0.039 ( 2280 hom. )
Consequence
VWF
NM_000552.5 intron
NM_000552.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.11
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 12-6095449-T-G is Benign according to our data. Variant chr12-6095449-T-G is described in ClinVar as [Benign]. Clinvar id is 256691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6095449-T-G is described in Lovd as [Benign]. Variant chr12-6095449-T-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.657+11A>C | intron_variant | ENST00000261405.10 | |||
VWF | XM_047429501.1 | c.657+11A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.657+11A>C | intron_variant | 1 | NM_000552.5 | P1 | |||
VWF | ENST00000321023.5 | c.*727A>C | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 1 | ||||
VWF | ENST00000538635.5 | n.420+15066A>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0996 AC: 15135AN: 151956Hom.: 1615 Cov.: 31
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GnomAD3 exomes AF: 0.0459 AC: 11540AN: 251480Hom.: 763 AF XY: 0.0411 AC XY: 5580AN XY: 135918
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GnomAD4 exome AF: 0.0392 AC: 57340AN: 1461778Hom.: 2280 Cov.: 31 AF XY: 0.0386 AC XY: 28066AN XY: 727196
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GnomAD4 genome ? AF: 0.0998 AC: 15180AN: 152074Hom.: 1623 Cov.: 31 AF XY: 0.0962 AC XY: 7151AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
von Willebrand disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
von Willebrand disease type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 18, 2019 | - - |
von Willebrand disease type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Hereditary von Willebrand disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at