3-10142192-G-C
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000551.4(VHL):c.340+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,596,998 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000551.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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VHL | NM_000551.4 | c.340+5G>C | splice_region_variant, intron_variant | Intron 1 of 2 | ENST00000256474.3 | NP_000542.1 | ||
VHL | NM_001354723.2 | c.340+5G>C | splice_region_variant, intron_variant | Intron 1 of 2 | NP_001341652.1 | |||
VHL | NM_198156.3 | c.340+5G>C | splice_region_variant, intron_variant | Intron 1 of 1 | NP_937799.1 | |||
VHL | NR_176335.1 | n.410+5G>C | splice_region_variant, intron_variant | Intron 1 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00401 AC: 610AN: 152178Hom.: 15 Cov.: 33
GnomAD3 exomes AF: 0.0125 AC: 2715AN: 217310Hom.: 71 AF XY: 0.0138 AC XY: 1672AN XY: 121436
GnomAD4 exome AF: 0.00460 AC: 6648AN: 1444702Hom.: 190 Cov.: 32 AF XY: 0.00583 AC XY: 4191AN XY: 718988
GnomAD4 genome AF: 0.00400 AC: 609AN: 152296Hom.: 16 Cov.: 33 AF XY: 0.00516 AC XY: 384AN XY: 74472
ClinVar
Submissions by phenotype
not specified Benign:7
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340+5G>C in intron 1 of VHL: This variant is not expected to have clinical signi ficance because it has been identified in 4.5% (9/200) Southern Han Chinese chro mosomes by the 1000 Genomes Project (dbSNP rs61758376). -
not provided Benign:6
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This variant is associated with the following publications: (PMID: 8956040, 25563310, 19996202, 22462637, 27884173, 22799452, 26332594, 20034980, 25985138, 27527340, 19906784, 22438210, 27057652, 25078357, 27069690, 27439424, 20518900, 8730290, 9829911, 21972040) -
Von Hippel-Lindau syndrome Benign:5
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. -
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at