About VHL
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
VHL c.-77C>T, p.?
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen VHL VCEP v1.1.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BA1Stand alone
BA1 · stand alone
NM_000551.3:c.-77C>T has a GroupMax Filtering Allele Frequency of 0.0888 (8.88%) in gnomAD v4.1 and 0.0856 (8.56%) in gnomAD v2.1, far exceeding the VHL VCEP BA1 threshold of ≥0.0156% (≥1.56×10⁻⁴). This allele frequency is incompatible with a highly penetrant autosomal dominant disorder such as von Hippel-Lindau disease. The variant is also observed in 332 homozygotes in gnomAD v4.1.
BS1Strong
BS1 · strong
NM_000551.3:c.-77C>T has a GroupMax Filtering Allele Frequency of 0.0888 (8.88%) in gnomAD v4.1, far exceeding the VHL VCEP BS1 threshold of ≥0.00156% (≥1.56×10⁻⁵). The allele frequency is too high for a rare disease like von Hippel-Lindau syndrome.
Recorded classification: Benign
ClinGen VHL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VHL Version 1.1.0 v1.1.0 criteria-combination framework: matched Rule17 (1 Benign.Stand Alone) with applied criteria: BA1 stand-alone benign, BS1 strong; maps to Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
7,326 / 1,488,092 alleles
gnomAD v4.1: 7,326 / 1,488,092 alleles. Recorded AF 0.00492308. Recorded homozygote count 332.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0257254; MAF= 2.57254%, 805/31292 alleles, homozygotes = 36) and has highest observed frequency in the African/African American population (AF= 0.0908356; MAF= 9.08356%, 787/8664 alleles, homozygotes = 36); grpmax FAF= 0.0855752.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
3 reported laboratory submissions
2 Benign · 1 Likely benign.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104558409, n = 2 times).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen VHL VCEP v1.1.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 5 not met · 10 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000551.3:c.-77C>T meets BA1 (Stand-Alone) under VHL VCEP v1.1.0: GroupMax Filtering Allele Frequency of 8.88% in gnomAD v4.1 far exceeds the BA1 threshold of 0.0156%, establishing this variant as benign.
NM_000551.3:c.-77C>T also meets BS1 (Strong): GroupMax Filtering Allele Frequency of 8.88% far exceeds the BS1 threshold of 0.00156%, further supporting a benign classification.
NM_000551.3:c.-77C>T is observed in 332 homozygotes in gnomAD v4.1 and 36 homozygotes in gnomAD v2.1, incompatible with autosomal dominant von Hippel-Lindau disease with high penetrance.
ClinVar classifies this variant as Benign (Variation ID 256649; 2 clinical laboratories) and Likely benign (1 clinical laboratory).
No pathogenic or likely pathogenic criteria were met. PM2 was not met (frequency far exceeds PM2_Supporting threshold). PP3 was not met (no computational evidence of deleterious effect). PVS1, PS1, PM1, and PM5 are not applicable to this 5'UTR variant.
Under VHL VCEP v1.1.0 combination rules (Rule 17), BA1 alone is sufficient for a Benign classification. Overall classification: Benign.
No criteria match.
Met · 2
BA1 Stand aloneNM_000551.3:c.-77C>T has a GroupMax Filtering Allele Frequency of 0.0888 (8.88%) in gnomAD v4.1 and 0.0856 (8.56%) in gnomAD v2.1, far exceeding the VHL VCEP BA1 threshold of ≥0.0156% (≥1.56×10⁻⁴). This allele frequency is incompatible with a highly penetrant autosomal dominant disorder such as von Hippel-Lindau disease. The variant is also observed in 332 homozygotes in gnomAD v4.1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF=0.08882 (8.88%)
- 7326 alleles
- 332 homozygotes
- highest in AFR (AF=9.07%)
- gnomAD v2.1: grpmax FAF=0.08558 (8.56%)
- 805 alleles
- 36 homozygotes
- highest in AFR (AF=9.08%)
- VCEP BA1 threshold: ≥0.000156 (0.0156%) GroupMax FAF
Sources
BS1 StrongNM_000551.3:c.-77C>T has a GroupMax Filtering Allele Frequency of 0.0888 (8.88%) in gnomAD v4.1, far exceeding the VHL VCEP BS1 threshold of ≥0.00156% (≥1.56×10⁻⁵). The allele frequency is too high for a rare disease like von Hippel-Lindau syndrome. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF=0.08882 (8.88%)
- 7326/1488092 alleles
- VCEP BS1 threshold: ≥0.0000156 (0.00156%) GroupMax FAF
Sources
Not met · 5 · evaluated, threshold not reached
PM2 NM_000551.3:c.-77C>T is common in population databases. In gnomAD v4.1, the GroupMax Filtering Allele Frequency is 0.08882 (8.88%), far exceeding the VCEP PM2_Supporting threshold of ≤0.000156% (≤1.56×10⁻⁶). The variant is observed in 7,326 alleles including 332 homozygotes. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF=0.492%
- grpmax FAF=0.08882 (8.88%)
- 7326/1488092 alleles
- 332 homozygotes
- gnomAD v2.1: AF=2.57%
- grpmax FAF=0.08558 (8.56%)
- 805/31292 alleles
- 36 homozygotes
- VCEP PM2_Supporting threshold: ≤0.000156% GroupMax FAF
Sources
PP3 VHL VCEP PP3 requires REVEL ≥0.664 for missense variants or SpliceAI >0.5 + VarSeak class 4/5 for splice variants. NM_000551.3:c.-77C>T is a 5'UTR variant; REVEL is not applicable (no missense change). SpliceAI returned null scores (no splice prediction generated for this variant). No computational evidence supports a damaging effect. Details ▾Hide ▴
Evidence considered
- SpliceAI: max_delta=null
- no splicing prediction available for this 5'UTR variant
- REVEL: score=null
- not applicable to non-missense variants
- VCEP PP3 rule: requires REVEL ≥0.664 (missense) or SpliceAI >0.5 + VarSeak class 4/5 (splice)
Sources
BP4 VHL VCEP BP4 requires concordance of SpliceAI ≤0.1 and VarSeak Class 1/2 to assess lack of splicing impact. SpliceAI returned null scores for NM_000551.3:c.-77C>T, indicating no splice prediction could be generated for this 5'UTR variant. Without a SpliceAI score ≤0.1, BP4 cannot be applied per VCEP specifications. Details ▾Hide ▴
Evidence considered
- SpliceAI: max_delta=null
- no splicing prediction available
- VCEP BP4 rule: SpliceAI ≤0.1 + VarSeak Class 1/2
- VCEP instruction: SpliceAI score alone can be applied if VarSeak cannot accept the variant type
Still missing
- SpliceAI could not generate a prediction for this 5'UTR variant
- VarSeak data not available
Sources
BP7 VHL VCEP BP7 requires that BP4 be met first (lack of splicing impact) and that the PhyloP score be ≤0.2. BP4 was not met because SpliceAI returned null scores for this variant. Therefore BP7 cannot be applied. Additionally, PhyloP conservation data for this position have not been evaluated. Details ▾Hide ▴
Evidence considered
- BP4 not met: SpliceAI returned null scores
- cannot confirm lack of splicing impact
- VCEP BP7 rule: use BP4 code first
- if BP4 is met for lack of splice effect
- BP7 can be applied to intronic variants with PhyloP ≤0.2
Still missing
- PhyloP score not evaluated (BP4 prerequisite not met)
Sources
PS5 ClinVar classifies NM_000551.3:c.-77C>T as Benign (2 clinical laboratories) and Likely benign (1 clinical laboratory). PS5 requires a reputable source to report the variant as pathogenic, which is not the case. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 256649: Benign (2 labs)
- Likely benign (1 lab)
- Review status: criteria provided
- single submitter
Sources
Not assessed · 10 · no assessment recorded
PS2 No de novo observations have been reported for NM_000551.3:c.-77C>T. PS2/PM6 requires confirmed or assumed de novo occurrence with a VHL-spectrum phenotype. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar
- literature
- or curated databases for this variant
Still missing
- No de novo data available
PS3 No functional studies have been performed on NM_000551.3:c.-77C>T. The VHL VCEP functional assay documentation spreadsheet (HIF degradation, VBC complex stability, fibronectin binding/deposition assays) does not contain an entry for this variant. PS3 cannot be assigned without experimental evidence. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet reviewed
- variant not listed in any approved assay
- No variant-specific functional data in publications
Still missing
- No functional data available for this 5'UTR variant
Sources
vcep_vhl_functional_assay_svi_documentation25741868
PS4 No proband data with VHL-spectrum phenotype has been identified for NM_000551.3:c.-77C>T. The ClinVar submissions cite general guideline references rather than variant-specific case reports. PS4 requires proband counting with VCEP phenotype scoring, and no qualifying probands are available. Details ▾Hide ▴
Evidence considered
- ClinVar: Benign classification
- 3 submissions
- no expert panel review
- No variant-specific case reports in literature
Still missing
- No proband phenotype data available for PS4 point scoring
Sources
PM6 No assumed or confirmed de novo observations have been reported for NM_000551.3:c.-77C>T. PM6 requires de novo occurrence (without confirmation of parentage) with a VHL-spectrum phenotype per VCEP scoring. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar
- literature
- or curated databases for this variant
Still missing
- No de novo data available
PP1 No segregation data are available for NM_000551.3:c.-77C>T. PP1 requires co-segregation in affected family members with VHL-spectrum disease across meioses. Details ▾Hide ▴
Evidence considered
- No segregation data in ClinVar
- literature
- or curated databases for this variant
Still missing
- No segregation data available
BS2 VHL VCEP BS2 requires at least 3 individuals aged ≥65 years, unaffected, with full phenotyping and screening for absence of VHL-related cancers. While gnomAD v4.1 shows 332 homozygotes for this variant, suggesting tolerance of homozygous state, individual-level clinical phenotype data meeting VCEP BS2 criteria are not available from population databases. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 332 homozygotes
- suggesting homozygous state is tolerated
- VCEP BS2 requires ≥3 individuals ≥65yo with full VHL phenotyping and screening
Still missing
- No individual-level phenotype data from gnomAD homozygotes
- Cannot confirm age ≥65 or VHL-specific cancer screening status
Sources
BS3 No functional studies demonstrating a benign effect have been reported for NM_000551.3:c.-77C>T. The VHL VCEP functional assay documentation spreadsheet does not list this variant in any approved assay (VBC complex stability, HIF degradation, fibronectin binding/deposition). BS3 requires well-established functional studies showing no damaging effect. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet reviewed
- variant not listed in any approved assay
- No variant-specific functional data in publications
Still missing
- No functional data available for this 5'UTR variant
Sources
vcep_vhl_functional_assay_svi_documentation
BS4 No segregation data are available for NM_000551.3:c.-77C>T. BS4 requires lack of segregation in affected members of families per VHL VCEP specifications. The high population frequency itself suggests lack of segregation with disease, but formal family-based segregation data are not available. Details ▾Hide ▴
Evidence considered
- No segregation data in ClinVar
- literature
- or curated databases for this variant
Still missing
- No family-based segregation data available
BP2 VHL VCEP BP2 can be applied when a variant is observed in trans with a known pathogenic variant, in the homozygous state without VHL disease, or in cis/unknown phase with multiple pathogenic VHL variants. gnomAD v4.1 shows 332 homozygotes for c.-77C>T, strongly suggesting homozygosity is tolerated, but individual clinical data confirming absence of VHL disease or congenital polycythemia are not available. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 332 homozygotes observed
- VCEP BP2_Strong: homozygous state in individual without VHL disease or congenital polycythemia
Still missing
- Cannot confirm individual clinical phenotype of gnomAD homozygotes
- No individual-level data confirming absence of VHL disease or congenital polycythemia
Sources
BP5 No co-occurrence data with pathogenic variants in other genes are available for NM_000551.3:c.-77C>T. VHL VCEP BP5 requires two or more co-occurrences with pathogenic variants in a different gene that fully explain the patient's phenotype, with specific phenotype criteria. Details ▾Hide ▴
Evidence considered
- No co-occurrence data in ClinVar or literature for this variant
Still missing
- No co-occurrence data available
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000551.3:c.-77C>T is a substitution 77 nucleotides upstream of the initiation codon in the 5'UTR. PVS1 is reserved for null variants (nonsense, frameshift, canonical splice). This variant does not alter protein sequence and does not fall into any PVS1 null-variant bucket per ClinGen SVI PVS1 recommendations and VHL VCEP guidance. Details ▾Hide ▴
Evidence considered
- 5'UTR substitution (c.-77C>T)
- outside the coding sequence
- VCEP PVS1 rule: Do not apply PVS1 for truncations that occur prior to Codon 54
- pvs1_variant_assessment: variant_bucket='other'
- not a null variant
Sources
pvs1_gene_contextpvs1_variant_assessment
PS1 N/APS1 requires a different nucleotide change at the same amino acid position that has been classified as pathogenic. This is a 5'UTR variant with no protein consequence; there is no amino acid change to compare. No VCEP-classified pathogenic variant exists at this non-coding position. Details ▾Hide ▴
Evidence considered
- 5'UTR variant produces no amino acid change (NP_000542.1:p.?)
- VCEP PS1 rule: applied only to variants with VHL VCEP interpretation
Sources
PM1 N/AVHL VCEP PM1 rule applies to putative missense variants in known germline hotspots, key functional domains, or somatic hotspots with cancerhotspots.org evidence. NM_000551.3:c.-77C>T is a 5'UTR substitution; it is not a missense variant and does not fall within a coding region or functional domain. Details ▾Hide ▴
Evidence considered
- 5'UTR variant
- not a missense change
- Hotspots: residue not significant
- exact variant not listed
Sources
PM5 N/APM5 requires a novel missense change at an amino acid residue where a different pathogenic missense has been established. NM_000551.3:c.-77C>T is a 5'UTR substitution with no protein consequence. There is no amino acid residue to compare. pm5_candidates confirms variant is not eligible for classic PM5. Details ▾Hide ▴
Evidence considered
- 5'UTR variant
- no protein change (NP_000542.1:p.?)
- pm5_candidates: reason='variant class is not missense-like'
- recommendation='not_applicable'
Sources
pm5_candidatescspec ↗
PP2 VCEPVHL VCEP specifies PP2 is not applicable for this gene. gnomAD shows VHL is not intolerant to missense variation (Z score = -0.39), and benign/common missense variants exist. Additionally, this is a 5'UTR substitution, not a missense variant. Details ▾Hide ▴
Evidence considered
- VCEP: PP2 applicability = Not applicable
- VHL missense Z score = -0.39 (not intolerant to missense variation)
Sources
PP4 VCEPVHL VCEP specifies PP4 is not applicable. The VCEP instructs combining phenotype assessment with PS4 to avoid double counting probands. Details ▾Hide ▴
PP5 VCEPVHL VCEP specifies PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP1 VCEPVHL VCEP specifies BP1 is not applicable for this gene. Truncating variants account for only a portion of disease-causing variants in VHL. Details ▾Hide ▴
BP3 N/ANM_000551.3:c.-77C>T is a single-nucleotide substitution in the 5'UTR, not an in-frame deletion/insertion in a repetitive region. BP3 applies only to the 8x GXEEX repeat motif in VHL p30 (AA14-AA48), which is within the coding sequence. This variant lies 77 nucleotides upstream of the start codon. Details ▾Hide ▴
Evidence considered
- Single nucleotide substitution
- not an in-frame indel
- Located in 5'UTR
- not in the GXEEX coding repeat motif (AA14-AA48)
BP6 VCEPVHL VCEP specifies BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Identifiers
- Gene
- VHL
- Transcript
- NM_000551.3
- Coding (HGVS c.)
- NM_000551.3:c.-77C>T
- Protein (HGVS p.)
- NP_000542.1:p.?
- GRCh38
- chr3:10141771 C>T
- GRCh37
- chr3:10183455 C>T
- ClinVar
- 256649
- COSMIC
- COSV104558409
Gene diagram
Every interpreted variant in VHL, mapped onto the exon structure of NM_000551.3. Select a row to find it on the plot.
VHLNM_000551.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in VHL
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
7,326 / 1,488,092 alleles
AF 0.00492 · 332 homozygotes · FAF 0.0888
gnomAD v2.1
805 / 31,292 alleles
AF 0.0257 · 36 homozygotes · FAF 0.0856
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 0.0049 · 7326 / 1,488,092 alleles · 332 hom · FAF 0.089
| African/African American6471 / 71,370 | 0.091325 hom |
| Admixed American320 / 49,082 | 0.00654 hom |
| Remaining individuals367 / 57,666 | 0.00643 hom |
| Middle Eastern9 / 4,228 | 0.0021 |
| European (non-Finnish)153 / 1,098,908 | 0.00014 |
| South Asian5 / 82,202 | 6.1e-05 |
| Ashkenazi Jewish1 / 27,836 | 3.6e-05 |
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, East Asian.
gnomAD v2.1
AF 0.026 · 805 / 31,292 alleles · 36 hom · FAF 0.086
| African/African American787 / 8,664 | 0.09136 hom |
| Admixed American8 / 848 | 0.0094 |
| Remaining individuals7 / 1,086 | 0.0064 |
| European (non-Finnish)3 / 15,376 | 0.0002 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00492308; MAF= 0.49231%, 7326/1488092 alleles, homozygotes = 332) and has highest observed frequency in the African/African American population (AF= 0.0906683; MAF= 9.06683%, 6471/71370 alleles, homozygotes = 325); grpmax FAF= 0.0888216.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0257254; MAF= 2.57254%, 805/31292 alleles, homozygotes = 36) and has highest observed frequency in the African/African American population (AF= 0.0908356; MAF= 9.08356%, 787/8664 alleles, homozygotes = 36); grpmax FAF= 0.0855752.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 VHL VCEP PP3 requires REVEL ≥0.664 for missense variants or SpliceAI >0.5 + VarSeak class 4/5 for splice variants. NM_000551.3:c.-77C>T is a 5'UTR variant; REVEL is not applicable (no missense change). SpliceAI returned null scores (no splice prediction generated for this variant). No computational evidence supports a damaging effect. Details ▾Hide ▴
Evidence considered
- SpliceAI: max_delta=null
- no splicing prediction available for this 5'UTR variant
- REVEL: score=null
- not applicable to non-missense variants
- VCEP PP3 rule: requires REVEL ≥0.664 (missense) or SpliceAI >0.5 + VarSeak class 4/5 (splice)
Sources
BP4 VHL VCEP BP4 requires concordance of SpliceAI ≤0.1 and VarSeak Class 1/2 to assess lack of splicing impact. SpliceAI returned null scores for NM_000551.3:c.-77C>T, indicating no splice prediction could be generated for this 5'UTR variant. Without a SpliceAI score ≤0.1, BP4 cannot be applied per VCEP specifications. Details ▾Hide ▴
Evidence considered
- SpliceAI: max_delta=null
- no splicing prediction available
- VCEP BP4 rule: SpliceAI ≤0.1 + VarSeak Class 1/2
- VCEP instruction: SpliceAI score alone can be applied if VarSeak cannot accept the variant type
Still missing
- SpliceAI could not generate a prediction for this 5'UTR variant
- VarSeak data not available
Sources
BP7 VHL VCEP BP7 requires that BP4 be met first (lack of splicing impact) and that the PhyloP score be ≤0.2. BP4 was not met because SpliceAI returned null scores for this variant. Therefore BP7 cannot be applied. Additionally, PhyloP conservation data for this position have not been evaluated. Details ▾Hide ▴
Evidence considered
- BP4 not met: SpliceAI returned null scores
- cannot confirm lack of splicing impact
- VCEP BP7 rule: use BP4 code first
- if BP4 is met for lack of splice effect
- BP7 can be applied to intronic variants with PhyloP ≤0.2
Still missing
- PhyloP score not evaluated (BP4 prerequisite not met)
Sources
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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PMID 20301636 ↗Von Hippel-Lindau Syndrome.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 20664475 ↗The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer.Chen H et al. · 2010No paper-specific finding is recorded.
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PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013No paper-specific finding is recorded.
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PMID 24319509 ↗Canadian guideline on genetic screening for hereditary renal cell cancers.Reaume MN et al. · 2013No paper-specific finding is recorded.
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PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG Board of Directors · 2015No paper-specific finding is recorded.
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015No paper-specific finding is recorded.
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PMID 24893135 ↗Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.Lenders JW et al. · 2014No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
7,326 / 1,488,092 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
2 Benign · 1 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1527855755
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/256649/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-10183455-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-10141771-C-T?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000551.3%3Ac.-77C…
- OncoKB ↗www.oncokb.org/gene/VHL/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121597103
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00492308; MAF= 0.49231%, 7326/1488092 alleles, homozygotes = 332) and has highest observed frequency in the African/African American population (AF= 0.0906683; MAF= 9.06683%, 6471/71370 alleles, homozygotes = 325); grpmax FAF= 0.0888216.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0257254; MAF= 2.57254%, 805/31292 alleles, homozygotes = 36) and has highest observed frequency in the African/African American population (AF= 0.0908356; MAF= 9.08356%, 787/8664 alleles, homozygotes = 36); grpmax FAF= 0.0855752.
ClinVar
This variant has been reported in ClinVar as Benign (2 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 256649)
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV104558409, n = 2 times).