12-6063036-T-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_000552.5(VWF):āc.1451A>Gā(p.His484Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 1,612,716 control chromosomes in the GnomAD database, including 327,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H484N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000552.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.1451A>G | p.His484Arg | missense_variant | 13/52 | ENST00000261405.10 | |
VWF | XM_047429501.1 | c.1451A>G | p.His484Arg | missense_variant | 13/52 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.1451A>G | p.His484Arg | missense_variant | 13/52 | 1 | NM_000552.5 | P1 | |
VWF | ENST00000538635.5 | n.420+47479A>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.526 AC: 80019AN: 151984Hom.: 24308 Cov.: 32
GnomAD3 exomes AF: 0.621 AC: 155009AN: 249536Hom.: 50166 AF XY: 0.638 AC XY: 86153AN XY: 135070
GnomAD4 exome AF: 0.640 AC: 934494AN: 1460614Hom.: 303674 Cov.: 55 AF XY: 0.644 AC XY: 468245AN XY: 726682
GnomAD4 genome AF: 0.526 AC: 80033AN: 152102Hom.: 24306 Cov.: 32 AF XY: 0.532 AC XY: 39557AN XY: 74358
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | Allele frequency is common in at least one population database (frequency: 73.314% in gnomAD_ExomesFounderPop) based on the frequency threshold of 0.5% for this gene. Variant was observed in a homozygous state in population databases more than expected for disease. - |
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at