rs61758376
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_000551.4(VHL):c.340+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,444,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000551.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.340+5G>A | splice_region_variant, intron_variant | Intron 1 of 2 | ENST00000256474.3 | NP_000542.1 | ||
VHL | NM_001354723.2 | c.340+5G>A | splice_region_variant, intron_variant | Intron 1 of 2 | NP_001341652.1 | |||
VHL | NM_198156.3 | c.340+5G>A | splice_region_variant, intron_variant | Intron 1 of 1 | NP_937799.1 | |||
VHL | NR_176335.1 | n.410+5G>A | splice_region_variant, intron_variant | Intron 1 of 3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000485 AC: 7AN: 1444716Hom.: 0 Cov.: 32 AF XY: 0.00000417 AC XY: 3AN XY: 718998
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.340+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 1 in the VHL gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear. -
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