3-10141825-G-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000551.4(VHL):c.-23G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,536,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )
Consequence
VHL
NM_000551.4 5_prime_UTR
NM_000551.4 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.164
Genes affected
VHL (HGNC:12687): (von Hippel-Lindau tumor suppressor) This gene encodes a component of a ubiquitination complex. The encoded protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. In addition to oxygen-related gene expression, this protein plays a role in many other cellular processes including cilia formation, cytokine signaling, regulation of senescence, and formation of the extracellular matrix. Variants of this gene are associated with von Hippel-Lindau syndrome, pheochromocytoma, erythrocytosis, renal cell carcinoma, and cerebellar hemangioblastoma. [provided by RefSeq, Jun 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| VHL | NM_000551.4 | c.-23G>T | 5_prime_UTR_variant | 1/3 | ENST00000256474.3 | NP_000542.1 | ||
| VHL | NM_001354723.2 | c.-23G>T | 5_prime_UTR_variant | 1/3 | NP_001341652.1 | |||
| VHL | NM_198156.3 | c.-23G>T | 5_prime_UTR_variant | 1/2 | NP_937799.1 | |||
| VHL | NR_176335.1 | n.48G>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| VHL | ENST00000256474.3 | c.-23G>T | 5_prime_UTR_variant | 1/3 | 1 | NM_000551.4 | ENSP00000256474 | P1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 7.22e-7 AC: 1AN: 1384246Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 682020
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GnomAD4 genome 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384
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ClinVar
Not reported inComputational scores
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Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at