About GBA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
GBA1 c.1495G>C, p.(Val499Leu)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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 GBA1 VCEP v1.0.0. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM2Supporting
PM2 · supporting
This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency = 5.18e-05 (13/251,170 alleles, 0 homozygotes, grpmax FAF = 5.60e-05) and gnomAD v4.1 allele frequency = 4.15e-05 (67/1,613,020 alleles, 0 homozygotes, grpmax FAF = 3.75e-05). Both are well below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada v1.0.
PP3Supporting
PP3 · supporting
Multiple lines of computational evidence support a deleterious effect. The REVEL meta-predictor score is 0.733, which exceeds the commonly used threshold of 0.5 for predicting pathogenicity. SpliceAI predicts no splicing impact (max delta = 0.00), which is neutral for this criterion. The BayesDel score is 0.348 (below the 0.5 threshold), but the REVEL score provides sufficient in silico support at the supporting level.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ClinGen Parkinson's Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GBA1 Version 1.0.0 v1.0.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, PP3 supporting; combination = 2 supporting, which maps to VUS.
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
67 / 1,613,020 alleles
gnomAD v4.1: 67 / 1,613,020 alleles. Recorded AF 4.1537e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.17578e-05; MAF= 0.00518%, 13/251170 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000144542; MAF= 0.01445%, 5/34592 alleles, homozygotes = 0); grpmax FAF= 5.597e-05.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
5 reported laboratory submissions
2 Uncertain significance · 2 Likely pathogenic · 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 ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen GBA1 VCEP v1.0.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 18 not met · 3 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000157.4:c.1495G>C (p.Val499Leu) is a missense variant in GBA1, which encodes the lysosomal enzyme glucocerebrosidase. Biallelic pathogenic variants in GBA1 cause Gaucher disease (autosomal recessive); heterozygous variants are associated with increased risk for Parkinson disease.
This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency = 0.0052% (13/251,170 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency = 0.0042% (67/1,613,020 alleles, 0 homozygotes), meeting PM2_Supporting.
In silico analysis supports a deleterious effect: the REVEL meta-predictor score is 0.733, exceeding the commonly used threshold of 0.5. SpliceAI predicts no splicing impact (max delta = 0.00). The BayesDel score (0.348) is below threshold, resulting in partially conflicting computational evidence; PP3 is applied at the supporting level.
This variant has been reported in ClinVar (Variation ID 634558) with conflicting classifications: Uncertain significance (2 clinical laboratories), Likely pathogenic (2 clinical laboratories), and Likely benign (1 clinical laboratory). No ClinGen expert panel classification is available.
Functional studies referenced in the literature (PMID:10714667, PMID:12924289) suggest reduced glucocerebrosidase activity for the mature protein equivalent V460L, but full-text verification of these studies was not available at the time of assessment. PS3 is not assessed pending direct review of primary data.
The ClinGen Parkinson's Disease Expert Panel specification for GBA1 (v1.0.0) is an unstructured ruleset without specific criterion thresholds. The assessment therefore applies generic ACMG/AMP 2015 criteria (PMID:25741868).
Overall, the evidence applied includes PM2_Supporting and PP3_Supporting. No benign criteria were met. All remaining criteria (PVS1, PS1-PS5, PM1, PM5-PM6, PP1-PP2, PP4-PP5, BA1, BS1-BS4, BP1-BP2, BP4-BP7) were either not met, not assessed, or not applicable.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency = 5.18e-05 (13/251,170 alleles, 0 homozygotes, grpmax FAF = 5.60e-05) and gnomAD v4.1 allele frequency = 4.15e-05 (67/1,613,020 alleles, 0 homozygotes, grpmax FAF = 3.75e-05). Both are well below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0052%
- 13/251
- 170 alleles
- 0 homozygotes
- gnomAD v4.1: AF = 0.0042%
- 67/1
- 613
- 020 alleles
- gnomAD-Canada: absent
Sources
PP3 SupportingMultiple lines of computational evidence support a deleterious effect. The REVEL meta-predictor score is 0.733, which exceeds the commonly used threshold of 0.5 for predicting pathogenicity. SpliceAI predicts no splicing impact (max delta = 0.00), which is neutral for this criterion. The BayesDel score is 0.348 (below the 0.5 threshold), but the REVEL score provides sufficient in silico support at the supporting level. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.733 (>0.5 threshold)
- BayesDel score = 0.348 (<0.5 threshold)
- SpliceAI max delta = 0.00 (no splicing impact)
Still missing
- BayesDel score does not support deleterious effect
- in silico evidence is partially conflicting
Sources
Not met · 18 · evaluated, threshold not reached
PS2 PS2 requires a de novo occurrence with confirmed maternity and paternity. No de novo data were identified for this variant. GBA1-related Gaucher disease is autosomal recessive; de novo heterozygous occurrences are not consistent with the established disease mechanism. Details ▾Hide ▴
Still missing
- No de novo occurrence data available
- De novo not expected for autosomal recessive GBA1/Gaucher disease
PS4 PS4 requires statistically significant enrichment of the variant in affected individuals compared to controls. While this variant has been reported in Gaucher disease probands and ClinVar contains multiple submissions, no published case-control study with calculated odds ratio is available. The gnomAD population frequency is very low (AF ~0.005%), which provides context but does not by itself satisfy PS4 without a formal case-control comparison. Details ▾Hide ▴
Evidence considered
- ClinVar: conflicting classifications (US
- LP
- LB)
- no expert panel classification
- gnomAD: very low population frequency but no case-control OR available
Still missing
- No case-control study with odds ratio for this variant
Sources
PM1 PM1 requires location in a mutational hotspot or critical functional domain without benign variation. The GBA1 ClinGen Parkinson's Disease VCEP (v1.0.0) does not define a PM1 domain or hotspot. Although the variant lies within the catalytic domain of glucocerebrosidase, no statistical evidence of pathogenic variant clustering or formal VCEP-defined hotspot is available. Details ▾Hide ▴
Evidence considered
- Variant lies in catalytic domain of GBA1
- but no VCEP-defined PM1 hotspot or statistical evidence of clustering
Still missing
- No VCEP-defined mutational hotspot for PM1 in GBA1
Sources
PM6 PM6 requires a de novo occurrence with confirmed maternity and paternity. No de novo data were identified for this variant. Gaucher disease is autosomal recessive, making de novo heterozygous occurrences inconsistent with the established disease mechanism. Details ▾Hide ▴
Still missing
- No de novo data available
- De novo not expected for autosomal recessive Gaucher disease
PP1 PP1 requires cosegregation with disease in multiple affected family members. No systematic segregation analysis with sufficient informative meioses or LOD scores was identified for this variant. Limited family-based observations mentioned in exploratory sources are insufficient to meet PP1. Details ▾Hide ▴
Still missing
- No systematic segregation data with LOD scores available
PP2 PP2 requires a low rate of benign missense variation in the gene and that missense variants are a common mechanism of disease. While missense variants are a well-established mechanism for Gaucher disease, no gene-specific benign missense constraint data (e.g., Z-score, missense constraint metrics) were available to demonstrate a low rate of benign missense variation in GBA1. Details ▾Hide ▴
Evidence considered
- Missense variants are a known mechanism for GBA1/Gaucher disease
- but low benign missense rate not demonstrated
Still missing
- No GBA1-specific benign missense constraint data available
PP4 PP4 requires that the patient's phenotype or family history is highly specific for the disease. No patient-specific phenotypic or family history data were available for this assessment. Details ▾Hide ▴
Still missing
- No patient phenotype or family history data available
PP5 PP5 requires that a reputable source has classified the variant as pathogenic. ClinVar (Variation ID 634558) reports conflicting classifications: Uncertain significance (2 clinical laboratories), Likely pathogenic (2 clinical laboratories), and Likely benign (1 clinical laboratory). No ClinGen expert panel classification is available. The conflicting ClinVar submissions and absence of expert panel consensus preclude application of PP5. Details ▾Hide ▴
Evidence considered
- ClinVar: conflicting classifications — US (2 labs)
- LP (2 labs)
- LB (1 lab)
- no expert panel submission
Still missing
- No expert panel classification available
Sources
BA1 BA1 requires allele frequency >1% in population databases. This variant has an allele frequency of approximately 0.005% in gnomAD (v2.1: 5.18e-05; v4.1: 4.15e-05), which is far below the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.0052%
- v4.1 AF = 0.0042%
- both << 1%
Sources
BS1 BS1 requires allele frequency >0.3% in population databases. This variant has an allele frequency of approximately 0.005% in gnomAD (v2.1: 5.18e-05; v4.1: 4.15e-05), which is far below the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.0052%
- v4.1 AF = 0.0042%
- both << 0.3%
Sources
BS2 BS2 requires observation in a healthy adult in the homozygous state for a recessive disorder. This variant has zero homozygotes observed in gnomAD v2.1 (0/251,170) and gnomAD v4.1 (0/1,613,020). No evidence of homozygous healthy adults is available. Details ▾Hide ▴
BS3 BS3 requires well-established in vitro or in vivo functional studies showing no damaging effect. The available functional evidence (exploratory results referencing PMID:10714667 and PMID:12924289) indicates reduced glucocerebrosidase activity for the mature protein equivalent V460L, which is consistent with a damaging — not benign — effect. BS3 is therefore not applicable. Details ▾Hide ▴
Evidence considered
- Exploratory evidence suggests damaging functional effect (reduced enzyme activity)
BS4 BS4 requires lack of segregation in affected family members. No evidence of non-segregation was identified. The limited available evidence suggests cosegregation with disease rather than non-segregation. Details ▾Hide ▴
Still missing
- No non-segregation data available
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. In GBA1, both missense and truncating variants are well-established causes of Gaucher disease. Missense variants are a primary disease mechanism, not an exception. BP1 does not apply. Details ▾Hide ▴
Evidence considered
- GBA1/Gaucher disease is caused by both missense and truncating variants
- missense is a primary mechanism
BP2 BP2 requires observation in trans with a pathogenic variant for a dominant disorder, or in cis with a pathogenic variant in a recessive disorder in an unaffected individual. No phasing data are available for this variant, and given its extremely low frequency, such observations are unlikely to exist in current databases. Details ▾Hide ▴
Still missing
- No phasing/cis-trans data available
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. The REVEL meta-predictor score is 0.733, which strongly suggests a deleterious effect — directly contradicting BP4. BayesDel (0.348) is below 0.5, and SpliceAI delta is 0.00, but REVEL's prediction of damaging effect precludes application of BP4. Details ▾Hide ▴
Evidence considered
- REVEL = 0.733 (deleterious prediction contradicts BP4)
- BayesDel = 0.348
- SpliceAI max delta = 0.00
Sources
BP5 BP5 requires that the variant is found in a case with an alternate molecular basis for disease. No such evidence was identified. Details ▾Hide ▴
Still missing
- No alternate molecular basis data available
BP6 BP6 requires that a reputable source classifies the variant as benign. ClinVar reports conflicting classifications (US, LP, LB). One submitter classified as Likely benign, but the overall ClinVar classification is Uncertain significance, and no ClinGen expert panel has classified as benign. BP6 is not met. Details ▾Hide ▴
Evidence considered
- ClinVar: one LB submission but overall US
- no expert panel benign classification
Still missing
- No expert panel benign classification
Sources
Not assessed · 3 · no assessment recorded
PS1 PS1 requires a different nucleotide change at the same codon resulting in the same amino acid change (p.Val499Leu) with established pathogenicity. No such comparator variant with definitive pathogenic classification was identified in the evidence pipeline. Details ▾Hide ▴
Still missing
- No known pathogenic nucleotide change producing p.Val499Leu was identified
PS3 The exploratory evidence pipeline identified functional studies (PMID:10714667 Koprivica et al. 2000; PMID:12924289 Ronan et al. 2003) reporting reduced glucocerebrosidase activity for the mature protein equivalent V460L (p.Val499Leu). However, full-text articles for these PMIDs are not available in the case directory and could not be directly verified for variant-specific evidence. Without direct confirmation of assay methodology, effect magnitude, and variant identity in the full text, PS3 cannot be applied. Details ▾Hide ▴
Evidence considered
- Exploratory evidence suggested functional studies (PMID:10714667
- PMID:12924289) showing reduced enzyme activity for V460L
Still missing
- Full-text verification of PMID:10714667 and PMID:12924289 needed to confirm variant-specific functional evidence and effect magnitude
PS5 PS5 requires a pathogenic variant at the same codon from a reputable source. No such variant was identified for codon 499 (Val) of GBA1 through the evidence pipeline. Details ▾Hide ▴
Still missing
- No known pathogenic variant at codon 499 identified
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. This variant (c.1495G>C, p.Val499Leu) does not fall into any of the generic PVS1 null-variant buckets (nonsense, frameshift, canonical ±1,2 splice consensus, initiation codon, single/multi-exon deletion). Details ▾Hide ▴
Evidence considered
- Missense substitution
- not a null variant per PMC6185798 PVS1 decision tree
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM5 N/APM5 requires a different pathogenic missense change at the same amino acid residue. The automated PM5 candidate harvest (pm5_candidates.json) was unable to identify same-residue comparator variants. No pathogenic variant at GBA1 residue 499 (Val) with a different amino acid substitution was identified. Details ▾Hide ▴
Evidence considered
- No same-residue pathogenic comparator identified
Still missing
- No known pathogenic missense variant at codon 499 other than p.Val499Leu
Sources
pm5_candidates
BP3 N/ASkipped per instructions. BP3 applies to in-frame deletions/insertions in repetitive regions; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. This variant (c.1495G>C, p.Val499Leu) is a missense (non-synonymous) substitution and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- not synonymous
Identifiers
- Gene
- GBA1
- Transcript
- NM_000157.4
- Coding (HGVS c.)
- NM_000157.4:c.1495G>C
- Protein (HGVS p.)
- NP_000148.2:p.(Val499Leu)
- GRCh38
- chr1:155235205 C>G
- GRCh37
- chr1:155204996 C>G
- ClinVar
- 634558
Gene diagram
Every interpreted variant in GBA1, mapped onto the exon structure of NM_000157.4. Select a row to find it on the plot.
GBA1NM_000157.4
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 GBA1
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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
67 / 1,613,020 alleles
AF 4.15e-05 · 0 homozygotes · FAF 3.75e-05
gnomAD v2.1
13 / 251,170 alleles
AF 5.18e-05 · 0 homozygotes · FAF 5.6e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 4.2e-05 · 67 / 1,613,020 alleles · 0 hom · FAF 3.7e-05
| Admixed American5 / 59,866 | 8.4e-05 |
| Remaining individuals5 / 62,458 | 8e-05 |
| European (non-Finnish)56 / 1,179,718 | 4.7e-05 |
| African/African American1 / 74,638 | 1.3e-05 |
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 5.2e-05 · 13 / 251,170 alleles · 0 hom · FAF 5.6e-05
| Admixed American5 / 34,592 | 0.00014 |
| European (non-Finnish)8 / 113,456 | 7.1e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.1537e-05; MAF= 0.00415%, 67/1613020 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.35199e-05; MAF= 0.00835%, 5/59866 alleles, homozygotes = 0); grpmax FAF= 3.749e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.17578e-05; MAF= 0.00518%, 13/251170 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000144542; MAF= 0.01445%, 5/34592 alleles, homozygotes = 0); grpmax FAF= 5.597e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.733
- BayesDel
- 0.348
How the predictions were used
PP3 SupportingMultiple lines of computational evidence support a deleterious effect. The REVEL meta-predictor score is 0.733, which exceeds the commonly used threshold of 0.5 for predicting pathogenicity. SpliceAI predicts no splicing impact (max delta = 0.00), which is neutral for this criterion. The BayesDel score is 0.348 (below the 0.5 threshold), but the REVEL score provides sufficient in silico support at the supporting level. Details ▾Hide ▴
Evidence considered
- REVEL score = 0.733 (>0.5 threshold)
- BayesDel score = 0.348 (<0.5 threshold)
- SpliceAI max delta = 0.00 (no splicing impact)
Still missing
- BayesDel score does not support deleterious effect
- in silico evidence is partially conflicting
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. The REVEL meta-predictor score is 0.733, which strongly suggests a deleterious effect — directly contradicting BP4. BayesDel (0.348) is below 0.5, and SpliceAI delta is 0.00, but REVEL's prediction of damaging effect precludes application of BP4. Details ▾Hide ▴
Evidence considered
- REVEL = 0.733 (deleterious prediction contradicts BP4)
- BayesDel = 0.348
- SpliceAI max delta = 0.00
Sources
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. This variant (c.1495G>C, p.Val499Leu) is a missense (non-synonymous) substitution and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant
- not synonymous
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.733. BayesDel score = 0.348057.
8 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.Richards S et al. · 2015No paper-specific finding is recorded.
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PMID 27153395 ↗Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.Maxwell KN et al. · 2016No paper-specific finding is recorded.
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PMID 32658388 ↗GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort.Petrucci S et al. · 2020No paper-specific finding is recorded.
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PMID 34426522 ↗The genetic structure of the Turkish population reveals high levels of variation and admixture.Kars ME et al. · 2021No paper-specific finding is recorded.
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PMID 18197057 ↗Carrier screening in individuals of Ashkenazi Jewish descent.Gross SJ et al. · 2008No paper-specific finding is recorded.
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PMID 19888064 ↗ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent.2009No paper-specific finding is recorded.
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PMID 20301446 ↗Gaucher Disease.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 22577228 ↗A clinical and family history study of Parkinson's disease in heterozygous glucocerebrosidase mutation carriers.McNeill A et al. · 2012No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
67 / 1,613,020 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
2 Uncertain significance · 2 Likely pathogenic · 1 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots 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/1833089217
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/634558/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-155204996-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-155235205-C-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000157.4%3Ac.1495…
- OncoKB ↗www.oncokb.org/gene/GBA1/V499L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=GBA1+c.1495G%3EC
- Cancer hotspots ↗www.cancerhotspots.org/
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= 4.1537e-05; MAF= 0.00415%, 67/1613020 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 8.35199e-05; MAF= 0.00835%, 5/59866 alleles, homozygotes = 0); grpmax FAF= 3.749e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 5.17578e-05; MAF= 0.00518%, 13/251170 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000144542; MAF= 0.01445%, 5/34592 alleles, homozygotes = 0); grpmax FAF= 5.597e-05.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 634558)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.733. BayesDel score = 0.348057.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.