3-10146508-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000551.4(VHL):c.341-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★★).
Frequency
Consequence
NM_000551.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.341-6C>G | splice_region_variant, intron_variant | Intron 1 of 2 | ENST00000256474.3 | NP_000542.1 | ||
VHL | NM_001354723.2 | c.*18-3279C>G | intron_variant | Intron 2 of 2 | NP_001341652.1 | |||
VHL | NM_198156.3 | c.341-3279C>G | intron_variant | Intron 1 of 1 | NP_937799.1 | |||
VHL | NR_176335.1 | n.670-6C>G | splice_region_variant, intron_variant | Intron 2 of 3 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Chuvash polycythemia Uncertain:1
ACMG classification criteria: PM2 moderate -
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Uncertain:1
This sequence change falls in intron 1 of the VHL gene. It does not directly change the encoded amino acid sequence of the VHL protein. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 647733). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at