About GBA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
GBA1 c.1279G>A, p.(Glu427Lys)
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
PM1Supporting
PM1 · supporting
Residue Glu427 is located within the well-characterized catalytic domain of glucocerebrosidase (GBA1). The GBA1 ClinGen Parkinson's Disease VCEP v1.0.0 does not provide explicit domain-level specifications; however, under generic ACMG/AMP rules, location in a critical functional domain where multiple pathogenic missense variants cluster supports PM1 at a supporting level.
PM2Supporting
PM2 · supporting
This variant is present at very low frequency in population databases: gnomAD v2.1 AF=0.0159% (45/282,860 alleles) and gnomAD v4.1 AF=0.0193% (311/1,614,180 alleles), both below the 0.1% threshold for PM2. No homozygotes observed. Absent from gnomAD-Canada v1.0.
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: PM1 supporting, PM2 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
311 / 1,614,180 alleles
gnomAD v4.1: 311 / 1,614,180 alleles. Recorded AF 0.000192667. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159089; MAF= 0.01591%, 45/282860 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000263207; MAF= 0.02632%, 34/129176 alleles, homozygotes = 0); grpmax FAF= 0.00021135.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00021720243266724586, 4/18416 alleles, homozygotes = 0).
SpliceAI score
0.070 maximum delta
Recorded SpliceAI maximum delta score: 0.070. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
7 Uncertain significance.
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 · 12 not met · 10 not assessed · 3 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.1279G>A (p.Glu427Lys) is a missense variant in exon 9 of GBA1, located within the catalytic domain of glucocerebrosidase.
This variant is present at very low frequency in population databases: gnomAD v2.1 AF=0.0159% (45/282,860 alleles) and gnomAD v4.1 AF=0.0193% (311/1,614,180 alleles), with no homozygotes observed (PM2_Supporting).
The variant is located within the well-characterized catalytic domain of GBA1 where multiple pathogenic missense variants cluster (PM1_Supporting).
This variant has been reported in ClinVar as Uncertain significance by 7 clinical laboratories (ClinVar Variation ID: 493050), with no expert panel classification available.
In silico predictors are mixed: REVEL score is 0.579 (intermediate), BayesDel is 0.107 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.07). Multiple lines of computational evidence do not consistently support a pathogenic or benign interpretation (PP3 not met, BP4 not met).
Exploratory literature review identified potential functional evidence (PMID:10079102, PMID:15300782) reporting severely reduced glucocerebrosidase activity for E427K, and potential co-segregation evidence (PMID:9375849). However, full-text verification was not available in this case to confirm exact variant-specific data (PS3 and PP1 not assessed pending full-text review).
Applying generic ACMG/AMP 2015 combination rules: PM1_Supporting + PM2_Supporting = 2 supporting pathogenic criteria. No benign criteria are met. This is consistent with a final classification of Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM1 SupportingResidue Glu427 is located within the well-characterized catalytic domain of glucocerebrosidase (GBA1). The GBA1 ClinGen Parkinson's Disease VCEP v1.0.0 does not provide explicit domain-level specifications; however, under generic ACMG/AMP rules, location in a critical functional domain where multiple pathogenic missense variants cluster supports PM1 at a supporting level. Details ▾Hide ▴
Evidence considered
- Glu427 is within the GBA1 catalytic domain (UniProt P04062)
- multiple pathogenic missense variants reported at nearby residues
- exploratory search confirmed domain-level functional significance.
Still missing
- GBA1 VCEP v1.0.0 does not define explicit PM1 domain boundaries or strength thresholds
- domain assignment is based on generic knowledge of GBA1 structure.
Sources
PM2 SupportingThis variant is present at very low frequency in population databases: gnomAD v2.1 AF=0.0159% (45/282,860 alleles) and gnomAD v4.1 AF=0.0193% (311/1,614,180 alleles), both below the 0.1% threshold for PM2. No homozygotes observed. Absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.000159 (45/282
- 860 alleles
- 0 homozygotes)
- gnomAD v4.1: AF=0.000193 (311/1
- 614
- 180 alleles
- gnomAD-Canada: absent
Sources
Not met · 12 · evaluated, threshold not reached
PS2 No published de novo occurrence of GBA1 c.1279G>A with confirmed parentage was identified in ClinVar or the available literature. Details ▾Hide ▴
Evidence considered
- ClinVar shows no de novo submissions
- exploratory literature search found no confirmed de novo reports.
Sources
PM6 No published de novo occurrence of GBA1 c.1279G>A (with or without paternity confirmation) was identified in ClinVar or the available literature. Details ▾Hide ▴
Evidence considered
- ClinVar contains no de novo submissions for this variant
- exploratory search found no assumed de novo cases.
Sources
PP3 Multiple lines of computational evidence do not consistently support a deleterious effect. REVEL score is 0.579 (intermediate, below typical pathogenic threshold), BayesDel score is 0.107 (benign-leaning), and SpliceAI predicts no significant splicing impact (max delta = 0.07). HCI prior is not available for GBA1. Details ▾Hide ▴
Evidence considered
- REVEL: 0.579 (intermediate
- below typical 0.7–0.75 pathogenic threshold)
- BayesDel: 0.107 (benign-leaning)
- SpliceAI max delta: 0.07 (no splicing impact predicted)
- HCI prior: not available for GBA1
Sources
PP5 ClinVar reports this variant as Uncertain significance (7 clinical laboratories, review status: criteria provided, single submitter). No reputable source has reported the variant as pathogenic. The ACMG/AMP guideline paper (PMID:25741868) and Sherloc paper (PMID:28492532) are methodological references and do not classify this specific variant. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (7 labs
- single submitter review)
- No expert panel pathogenic classification
- PMID:25741868 and PMID:28492532 are methodological references
- not variant-specific classifications
Sources
BA1 The variant allele frequency in gnomAD (v2.1: 0.0159%; v4.1: 0.0193%) is far below the BA1 threshold of >1% (non-VCEP) or >5% (generic ACMG/AMP). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF: 0.000159 (0.0159%)
- gnomAD v4.1 AF: 0.000193 (0.0193%)
Sources
BS1 The variant allele frequency in gnomAD (v2.1: 0.0159%; v4.1: 0.0193%) is below the non-VCEP BS1 threshold of >0.3%. The frequency is not greater than expected for Gaucher disease or Parkinson's disease risk. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF: 0.000159 (0.0159%)
- gnomAD v4.1 AF: 0.000193 (0.0193%)
Sources
BS2 No homozygous observations of this variant are reported in gnomAD v2.1 or v4.1. The variant has not been observed in a healthy adult in the homozygous state. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0 homozygotes
- gnomAD v4.1: 0 homozygotes
Sources
BS3 Published functional studies identified in the exploratory search (PMID:10079102, PMID:15300782) report a damaging effect (severely reduced enzyme activity) for E427K, not a benign effect. No well-established functional study indicates a benign effect for this variant. Details ▾Hide ▴
Evidence considered
- Exploratory search identified functional studies showing damaging effect (<10% WT activity)
- no studies report benign functional impact.
Still missing
- Full-text verification for functional studies (PMID:10079102
- PMID:15300782) pending.
BP1 GBA1 missense variants are a well-established cause of both autosomal recessive Gaucher disease and Parkinson's disease risk. The gene is not one in which only truncating variants cause disease. Details ▾Hide ▴
Evidence considered
- GBA1 missense variants (e.g.
- N409S
- L483P
- E365K) are established pathogenic risk factors
- missense mechanism is well-characterized in Gaucher disease.
Sources
BP2 GBA1 is associated with autosomal recessive Gaucher disease. No observation of this variant in cis with a pathogenic variant in a healthy individual, or in trans with a pathogenic variant for a fully penetrant dominant disorder, was identified to support BP2. Exploratory search suggests the variant may be observed in trans with pathogenic alleles in Gaucher disease patients (PMID:9375849), which would support pathogenicity rather than benignity. Details ▾Hide ▴
Evidence considered
- GBA1 inheritance is autosomal recessive for Gaucher disease
- no cis or trans observations support benign effect.
BP4 Multiple lines of computational evidence do not consistently suggest no impact. While BayesDel (0.107) is benign-leaning and SpliceAI (max delta 0.07) predicts no splicing impact, REVEL (0.579) is intermediate and does not clearly support a benign interpretation. The computational evidence is mixed rather than consistently benign. Details ▾Hide ▴
Evidence considered
- REVEL: 0.579 (intermediate
- not clearly benign)
- BayesDel: 0.107 (benign-leaning)
- SpliceAI max delta: 0.07 (no splicing impact)
Sources
BP6 ClinVar reports this variant as Uncertain significance (7 clinical laboratories). No reputable source has reported the variant as benign or likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (7 labs)
- no benign or likely benign classifications from any submitter.
Sources
Not assessed · 10 · no assessment recorded
PS1 No evidence was identified for a different nucleotide change at the same codon producing the same amino acid change (p.Glu427Lys) that has been previously classified as pathogenic. Details ▾Hide ▴
Still missing
- No nucleotide-level comparator variants at codon 427 producing p.Glu427Lys were identified in ClinVar or the literature.
PS3 Exploratory literature search identified two functional studies (PMID:10079102 Grace et al. 1999; PMID:15300782 Montfort et al. 2004) reporting E427K resulting in <10% wild-type glucocerebrosidase activity in heterologous expression systems. However, full-text verification was not available in this case to confirm the exact variant data, assay validation, and experimental details required to apply PS3. Details ▾Hide ▴
Evidence considered
- Exploratory subagent identified PMID:10079102 and PMID:15300782 reporting severely reduced enzyme activity for E427K in COS-7 cells and independent functional assays.
Still missing
- Full-text verification needed for PMID:10079102 (Grace et al. 1999) to confirm residual activity and assay validation.
- Full-text verification needed for PMID:15300782 (Montfort et al. 2004) to confirm independent functional evidence.
- Neither PMID was available in the case full-text corpus nor in publications.json abstracts.
PS4 No case-control study directly comparing the prevalence of GBA1 c.1279G>A in affected individuals versus controls was identified. Several cohort studies (PMID:25249066, PMID:32658388, PMID:32618053) screened GBA1 in Parkinson's disease cohorts, but full-text verification was not available to confirm whether c.1279G>A was observed and at what frequency. Details ▾Hide ▴
Evidence considered
- ClinVar-associated PMIDs reference GBA1 cohort studies
- but variant-specific case counts could not be confirmed from available abstracts.
Still missing
- Full-text review needed for PMID:25249066
- PMID:32658388
- PMID:32618053
- PMID:23035075
- PMID:23588557 to extract variant-specific case counts.
- No dedicated case-control study comparing c.1279G>A prevalence in affected vs. controls was identified.
PM5 PM5 candidate harvesting was unable to confirm classic same-residue PM5 semantics safely. No same-residue comparator variants (different amino acid change at Glu427) with pathogenic classification were identified in ClinVar. Details ▾Hide ▴
Evidence considered
- PM5 candidate search returned zero same-residue candidates
- eligibility for classic PM5 search was not met.
Still missing
- No known pathogenic missense changes at codon 427 other than Glu427Lys in ClinVar.
PP1 Exploratory literature search identified a report (PMID:9375849, Ida et al. 1997) of a Japanese family with Gaucher disease where multiple affected siblings carried E427K co-segregating with the disease phenotype. However, full-text verification was not available in this case to confirm the number of meioses and segregation pattern. Details ▾Hide ▴
Evidence considered
- Exploratory subagent identified PMID:9375849 reporting co-segregation of E427K with Gaucher disease in a Japanese family.
Still missing
- Full-text verification needed for PMID:9375849 to assess family structure
- number of affected meioses
- and statistical significance of co-segregation.
- PMID:9375849 was not available in the case full-text corpus or source_registry.
PP2 PP2 requires demonstration that the gene has a low rate of benign missense variation and that missense variants are a common disease mechanism. GBA1 is known to have many pathogenic missense variants associated with both autosomal recessive Gaucher disease and Parkinson's disease risk. However, gene-level missense constraint metrics (e.g., missense Z-score, o/e ratio) were not provided in this case, and the GBA1 VCEP does not specify PP2 rules. Details ▾Hide ▴
Evidence considered
- GBA1 missense variants are an established disease mechanism for Gaucher disease and Parkinson's disease risk.
Still missing
- Gene-level missense constraint data (missense Z-score
- o/e ratio) not available
- VCEP does not define PP2 applicability.
PP4 No detailed phenotype or family history information specific to the proband was provided in this case to assess whether the variant's phenotype is highly specific for the disease. Details ▾Hide ▴
Still missing
- No proband-specific phenotype or clinical history available for PP4 assessment.
BS4 No family studies demonstrating lack of segregation of c.1279G>A with disease phenotype were identified. The exploratory search found potential co-segregation evidence (PMID:9375849) supporting pathogenicity, not benignity. Details ▾Hide ▴
Evidence considered
- Exploratory search identified co-segregation rather than non-segregation evidence.
Still missing
- No non-segregation data available.
BP5 No case was identified in which this variant is found in an individual with an alternate molecular basis for disease, while the individual's phenotype or family history is specific for the gene-associated condition. Details ▾Hide ▴
Still missing
- No alternate-molecular-basis cases identified.
PS5 No different missense change at residue 427 with an established pathogenic classification was identified for comparison. PM5 candidate harvesting found no same-residue comparator variants with confirmed pathogenic status. Details ▾Hide ▴
Evidence considered
- PM5 candidate search returned zero same-residue candidates with expert panel or majority pathogenic classification.
Still missing
- No ClinVar entries for other missense changes at codon 427 (Glu427) with pathogenic classification.
Not applicable · 3· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000157.4:c.1279G>A is a missense variant (p.Glu427Lys) and does not fall into the null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants required for PVS1 application per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense variant
- variant bucket 'other'
- apply_generic_pvs1_framework=false.
Sources
BP3 N/ABP3 applies to in-frame insertions/deletions in repetitive regions; NM_000157.4:c.1279G>A is a single-nucleotide substitution (missense). Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. NM_000157.4:c.1279G>A is a missense variant (p.Glu427Lys), not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- GBA1
- Transcript
- NM_000157.4
- Coding (HGVS c.)
- NM_000157.4:c.1279G>A
- Protein (HGVS p.)
- NP_000148.2:p.(Glu427Lys)
- GRCh38
- chr1:155235790 C>T
- GRCh37
- chr1:155205581 C>T
- ClinVar
- 493050
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
311 / 1,614,180 alleles
AF 0.000193 · 0 homozygotes · FAF 0.0002
gnomAD v2.1
45 / 282,860 alleles
AF 0.000159 · 0 homozygotes · FAF 0.000211
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00019 · 311 / 1,614,180 alleles · 0 hom · FAF 0.0002
| European (non-Finnish)263 / 1,180,044 | 0.00022 |
| South Asian20 / 91,084 | 0.00022 |
| Remaining individuals13 / 62,506 | 0.00021 |
| Middle Eastern1 / 6,062 | 0.00016 |
| European (Finnish)9 / 64,038 | 0.00014 |
| Admixed American4 / 60,024 | 6.7e-05 |
| African/African American1 / 75,016 | 1.3e-05 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00016 · 45 / 282,860 alleles · 0 hom · FAF 0.00021
| European (non-Finnish)34 / 129,176 | 0.00026 |
| Remaining individuals1 / 7,226 | 0.00014 |
| South Asian4 / 30,616 | 0.00013 |
| European (Finnish)3 / 25,120 | 0.00012 |
| Admixed American2 / 35,432 | 5.6e-05 |
| African/African American1 / 24,966 | 4e-05 |
0 alternate alleles recorded in 2 other groups: Ashkenazi Jewish, East Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000192667; MAF= 0.01927%, 311/1614180 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000222873; MAF= 0.02229%, 263/1180044 alleles, homozygotes = 0); grpmax FAF= 0.00020027.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159089; MAF= 0.01591%, 45/282860 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000263207; MAF= 0.02632%, 34/129176 alleles, homozygotes = 0); grpmax FAF= 0.00021135.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00021720243266724586, 4/18416 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.579
- BayesDel
- 0.107
How the predictions were used
PP3 Multiple lines of computational evidence do not consistently support a deleterious effect. REVEL score is 0.579 (intermediate, below typical pathogenic threshold), BayesDel score is 0.107 (benign-leaning), and SpliceAI predicts no significant splicing impact (max delta = 0.07). HCI prior is not available for GBA1. Details ▾Hide ▴
Evidence considered
- REVEL: 0.579 (intermediate
- below typical 0.7–0.75 pathogenic threshold)
- BayesDel: 0.107 (benign-leaning)
- SpliceAI max delta: 0.07 (no splicing impact predicted)
- HCI prior: not available for GBA1
Sources
BP4 Multiple lines of computational evidence do not consistently suggest no impact. While BayesDel (0.107) is benign-leaning and SpliceAI (max delta 0.07) predicts no splicing impact, REVEL (0.579) is intermediate and does not clearly support a benign interpretation. The computational evidence is mixed rather than consistently benign. Details ▾Hide ▴
Evidence considered
- REVEL: 0.579 (intermediate
- not clearly benign)
- BayesDel: 0.107 (benign-leaning)
- SpliceAI max delta: 0.07 (no splicing impact)
Sources
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. NM_000157.4:c.1279G>A is a missense variant (p.Glu427Lys), not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.579. BayesDel score = 0.107037.
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 22820396 ↗First pilot newborn screening for four lysosomal storage diseases in an Italian region: identification and analysis of a putative causative mutation in the GBA gene.Paciotti S et al. · 2012No paper-specific finding is recorded.
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PMID 25249066 ↗Glucocerebrosidase mutations in primary parkinsonism.Asselta R et al. · 2014No paper-specific finding is recorded.
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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. · 2015Joint consensus recommendation from ACMG and AMP establishing standards and guidelines for the interpretation of sequence variants. Provides the generic ACMG/AMP variant classification framework and five-tier terminology. Does not classify or comment on any specific GBA1 variant.Does not name this variant
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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 23035075 ↗GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology.Tsuang D et al. · 2012No paper-specific finding is recorded.
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PMID 23588557 ↗A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies.Nalls MA et al. · 2013No paper-specific finding is recorded.
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PMID 30302829 ↗Coding variation in GBA explains the majority of the SYT11-GBA Parkinson's disease GWAS locus.Blauwendraat C et al. · 2018No paper-specific finding is recorded.
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PMID 32618053 ↗A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands.den Heijer JM et al. · 2020No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Comprehensive refinement of the ACMG-AMP variant classification criteria (Sherloc system) developed through iterative classification of over 40,000 clinically observed variants. Introduces semiquantitative scoring and separates ambiguous criteria into discrete rules. Does not classify or comment on any specific GBA1 variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
311 / 1,614,180 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.070
Open source ↗
ClinVar
7 Uncertain significance
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/493050/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-155205581-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-155235790-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/1-155235790-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000157.4%3Ac.1279…
- OncoKB ↗www.oncokb.org/gene/GBA1/E427K
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=GBA1+c.1279G%3EA
- 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= 0.000192667; MAF= 0.01927%, 311/1614180 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000222873; MAF= 0.02229%, 263/1180044 alleles, homozygotes = 0); grpmax FAF= 0.00020027.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159089; MAF= 0.01591%, 45/282860 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000263207; MAF= 0.02632%, 34/129176 alleles, homozygotes = 0); grpmax FAF= 0.00021135.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00021720243266724586, 4/18416 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories). (ClinVarID = 493050)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07). REVEL score = 0.579. BayesDel score = 0.107037.
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.