rs10622288
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000552.5(VWF):c.1946-15_1946-14insTCT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,609,740 control chromosomes in the GnomAD database, including 580,553 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.85 ( 55266 hom., cov: 0)
Exomes 𝑓: 0.85 ( 525287 hom. )
Consequence
VWF
NM_000552.5 splice_polypyrimidine_tract, intron
NM_000552.5 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.20
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 -16 ACMG points.
BP6
Variant 12-6052797-G-GAGA is Benign according to our data. Variant chr12-6052797-G-GAGA is described in ClinVar as [Likely_benign]. Clinvar id is 256657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.1946-15_1946-14insTCT | splice_polypyrimidine_tract_variant, intron_variant | ENST00000261405.10 | NP_000543.3 | |||
VWF | XM_047429501.1 | c.1946-15_1946-14insTCT | splice_polypyrimidine_tract_variant, intron_variant | XP_047285457.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.1946-15_1946-14insTCT | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000552.5 | ENSP00000261405 | P1 | |||
VWF | ENST00000538635.5 | n.420+57717_420+57718insTCT | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.852 AC: 129367AN: 151828Hom.: 55230 Cov.: 0
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GnomAD3 exomes AF: 0.841 AC: 202052AN: 240314Hom.: 85059 AF XY: 0.838 AC XY: 109155AN XY: 130200
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GnomAD4 exome AF: 0.848 AC: 1236714AN: 1457792Hom.: 525287 Cov.: 60 AF XY: 0.846 AC XY: 613360AN XY: 724874
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GnomAD4 genome AF: 0.852 AC: 129455AN: 151948Hom.: 55266 Cov.: 0 AF XY: 0.852 AC XY: 63236AN XY: 74252
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 25, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
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 | - - |
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
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at