3-10142093-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4BP6_Very_StrongBP7
The NM_000551.4(VHL):c.246C>T(p.Arg82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,604,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
VHL
NM_000551.4 synonymous
NM_000551.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.11).
BP6
?
Variant 3-10142093-C-T is Benign according to our data. Variant chr3-10142093-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.16 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VHL | NM_000551.4 | c.246C>T | p.Arg82= | synonymous_variant | 1/3 | ENST00000256474.3 | |
VHL | NM_001354723.2 | c.246C>T | p.Arg82= | synonymous_variant | 1/3 | ||
VHL | NM_198156.3 | c.246C>T | p.Arg82= | synonymous_variant | 1/2 | ||
VHL | NR_176335.1 | n.316C>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VHL | ENST00000256474.3 | c.246C>T | p.Arg82= | synonymous_variant | 1/3 | 1 | NM_000551.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000100 AC: 23AN: 229092Hom.: 0 AF XY: 0.0000865 AC XY: 11AN XY: 127116
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GnomAD4 exome AF: 0.000258 AC: 375AN: 1452208Hom.: 0 Cov.: 32 AF XY: 0.000246 AC XY: 178AN XY: 722734
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Von Hippel-Lindau syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Dec 01, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 31, 2015 | This alteration is classified as likely 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 21, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Von Hippel-Lindau syndrome;C1837915:Chuvash polycythemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at