About HNF1A
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
HNF1A c.341G>A, p.(Arg114His)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely 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 HNF1A VCEP v3.1.0. 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: 1
Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM1Supporting
PM1 · supporting
Codon 114 lies within the DNA binding domain subset (codons 107-174) defined by the HNF1A CSPEC for PM1_Supporting. The variant is not in the directly DNA-binding residue list for PM1_Moderate. Located in a statistically significant hotspot (evidence_brief).
Benign criteria applied · 2
BS1Strong
BS1 · strong
CSPEC BS1_Strong requires gnomAD grpmax FAF ≥ 1:30,000 (≥ 0.000033). The variant has gnomAD v2.1 grpmax FAF of 9.374e-05, which exceeds this threshold by approximately 2.8-fold. This allele frequency is greater than expected for HNF1A-MODY, a rare monogenic disorder.
BS3Supporting
BS3 · supporting
CSPEC BS3_Supporting requires luciferase transactivation assay showing ≥ 75% of wild-type activity. In PMID:27899486 (Najmi et al. 2017), the p.Arg114His variant demonstrated 83% transactivation activity compared to wild-type in a validated luciferase reporter assay in transfected HeLa cells, with normal nuclear localization (81% of cells with nuclear accumulation). This meets the CSPEC threshold for benign functional evidence.
Recorded classification: Likely benign
ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 3.1.0 v3.1.0 criteria-combination framework: matched Rule18 (1 Benign.Strong + 1 Benign.Supporting) with applied criteria: PM1 supporting, BS1 strong benign, BS3 supporting benign; maps to Likely 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
78 / 1,614,100 alleles
gnomAD v4.1: 78 / 1,614,100 alleles. Recorded AF 4.83241e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95256e-05; MAF= 0.00495%, 14/282682 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160321; MAF= 0.01603%, 4/24950 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
6 reported laboratory submissions
5 Uncertain significance · 1 Likely benign.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
10 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV57459115, n = 10 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen HNF1A VCEP v3.1.0, with the data and sources behind each one.
27 criteria with recorded statuses: 3 met · 15 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000545.6:c.341G>A (p.Arg114His) is a missense variant in HNF1A, a gene in which loss-of-function variants cause autosomal dominant monogenic diabetes (MODY3).
This variant is present in gnomAD v2.1 at a grpmax filtering allele frequency of 9.374e-05 (14/282,682 alleles) and in gnomAD v4.1 at 4.428e-05 (78/1,614,100 alleles), exceeding the CSPEC BS1_Strong threshold of 1:30,000 (0.000033).
Functional characterization by Najmi et al. (2017) demonstrated that p.Arg114His retains 83% of wild-type transactivation activity in a luciferase reporter assay and shows normal nuclear localization (81%), meeting the CSPEC BS3_Supporting threshold of ≥75% activity.
The variant is located at codon 114, which lies within the CSPEC-defined DNA binding domain subset (codons 107-174), supporting application of PM1_Supporting. However, Arg114 is not among the directly DNA-binding residues specified for PM1_Moderate.
In silico predictions are indeterminate: REVEL score is 0.58 (below the CSPEC PP3 threshold of 0.70; above the BP4 threshold of 0.15); SpliceAI predicts no splicing impact (max delta 0.01).
The variant has been reported in ClinVar as Uncertain significance by 5 clinical laboratories and Likely benign by 1 laboratory (VariationID: 134508). No expert panel classification is available.
Applying the CSPEC v3.1.0 combination rules: BS1 (Strong Benign) and BS3 (Supporting Benign) are met on the benign side, while PM1 (Supporting Pathogenic) is met on the pathogenic side. Per Rule 24 (≥1 Benign Strong + ≥1 Pathogenic Supporting), the evidence is conflicting, resulting in a classification of Uncertain Significance.
No criteria match.
Met · 3
PM1 SupportingCodon 114 lies within the DNA binding domain subset (codons 107-174) defined by the HNF1A CSPEC for PM1_Supporting. The variant is not in the directly DNA-binding residue list for PM1_Moderate. Located in a statistically significant hotspot (evidence_brief). Details ▾Hide ▴
Evidence considered
- Residue Arg114 falls within CSPEC-defined DNA binding domain region (codons 107-174)
- PM1_Supporting applies
Sources
BS1 StrongCSPEC BS1_Strong requires gnomAD grpmax FAF ≥ 1:30,000 (≥ 0.000033). The variant has gnomAD v2.1 grpmax FAF of 9.374e-05, which exceeds this threshold by approximately 2.8-fold. This allele frequency is greater than expected for HNF1A-MODY, a rare monogenic disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF = 9.374e-05 (14/282682 alleles
- 0 homozygotes)
- gnomAD v4.1 grpmax FAF = 4.428e-05 (78/1614100 alleles
- highest exceeds CSPEC BS1 threshold of 0.000033
Sources
BS3 SupportingCSPEC BS3_Supporting requires luciferase transactivation assay showing ≥ 75% of wild-type activity. In PMID:27899486 (Najmi et al. 2017), the p.Arg114His variant demonstrated 83% transactivation activity compared to wild-type in a validated luciferase reporter assay in transfected HeLa cells, with normal nuclear localization (81% of cells with nuclear accumulation). This meets the CSPEC threshold for benign functional evidence. Details ▾Hide ▴
Evidence considered
- Luciferase transactivation assay in HeLa cells: 83% of wild-type activity (≥ 75% BS3 threshold)
- nuclear localization: 81% (normal)
Sources
Not met · 15 · evaluated, threshold not reached
PS1 No previously classified pathogenic variant encoding the same amino acid change (p.Arg114His) has been identified. No same-residue pathogenic comparator is available in the CSPEC framework. Details ▾Hide ▴
Still missing
- No same amino acid change previously classified as pathogenic by ClinGen MDEP specifications
PS2 No de novo occurrence data are available for this variant. No proband with confirmed parental relationships has been reported in the reviewed literature. Details ▾Hide ▴
Still missing
- No de novo observations reported
PS3 CSPEC PS3_Supporting requires transactivation ≤40% of wild-type. The variant p.Arg114His demonstrated 83% transactivation activity in a luciferase reporter assay (PMID:27899486), which does not meet the threshold for damaging functional effect. CSPEC PS3_Moderate requires ≤40% transactivation by Gloyn/Oxford group; not applicable here. Details ▾Hide ▴
Evidence considered
- Transactivation assay (HeLa cells): 83% of wild-type activity
- well above the 40% pathogenic threshold
Sources
PS4 CSPEC requires PM2_Supporting as a prerequisite for applying PS4 at any level. PM2 is not met (gnomAD grpmax FAF 9.374e-05 exceeds the 3.0e-06 threshold). Additionally, no systematic count of unrelated MODY probands with this variant is available in the reviewed evidence. Details ▾Hide ▴
Evidence considered
- PM2 prerequisite not satisfied
- gnomAD frequency too high to apply PS4
Still missing
- PS4 cannot be applied without PM2_Supporting per CSPEC rules
Sources
PM2 CSPEC PM2_Supporting requires gnomAD grpmax FAF ≤ 1:333,000 (≤ 0.000003). The highest observed grpmax FAF is 9.374e-05 (gnomAD v2.1), which exceeds this threshold. The variant is present in population databases at a frequency inconsistent with PM2. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF = 9.374e-05 (14/282682 alleles)
- gnomAD v4.1 grpmax FAF = 4.428e-05 (78/1614100 alleles)
- both exceed CSPEC PM2 threshold of 0.000003
Sources
PM5 No previously classified pathogenic or likely pathogenic missense variants at residue Arg114 were identified. The pm5_candidates search returned 0 same-residue comparator variants. Without a pathogenic comparator at this residue, PM5 cannot be applied. Details ▾Hide ▴
Evidence considered
- 0 same-residue pathogenic/likely pathogenic comparator variants found
Still missing
- No pathogenic comparator at residue 114 available
PP1 No cosegregation data are available for this variant. No family studies with meiotic counts were identified in the reviewed literature. Details ▾Hide ▴
Still missing
- No cosegregation data available
PP3 CSPEC PP3_Supporting requires REVEL score ≥ 0.70. The REVEL score for this variant is 0.58, which is below the threshold. SpliceAI max delta is 0.01, indicating no predicted splicing impact. BayesDel score is 0.007 (low). In silico tools do not support a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL = 0.58 (< 0.70 threshold)
- BayesDel = 0.007
- SpliceAI max delta = 0.01
Sources
PP4 No patient-specific phenotype data are available for this adjudication. CSPEC PP4 requires MODY Probability Calculator score ≥ 50%, negative HNF4A testing, and additional HNF1A-MODY features. No such clinical data were provided or identified in the literature. Details ▾Hide ▴
Still missing
- No patient phenotype data available for PP4 assessment
BA1 CSPEC BA1 requires gnomAD grpmax FAF ≥ 1:10,000 (≥ 0.0001). The highest observed grpmax FAF is 9.374e-05 (gnomAD v2.1), which is below the BA1 threshold. The variant is too rare in population databases to be considered a common polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF = 9.374e-05
- gnomAD v4.1 grpmax FAF = 4.428e-05
- both below BA1 threshold of 0.0001
Sources
BS2 CSPEC BS2 requires observation in normoglycemic individuals aged 70 or older. No such data are available in the reviewed evidence. The population cohort data in PMID:27899486 included individuals from Framingham Heart Study and Jackson Heart Study, but age-specific normoglycemic status is not reported for this variant. Details ▾Hide ▴
Still missing
- No data on normoglycemic individuals aged ≥70 carrying this variant
BS4 CSPEC BS4 applies to family members without the variant who have MPC score >50% (genotype-negative, phenotype-positive). No such segregation data are available for this variant. Details ▾Hide ▴
Still missing
- No segregation data available
BP2 No evidence that this variant has been observed in cis or in trans with a pathogenic or likely pathogenic HNF1A variant. No phase data available. Details ▾Hide ▴
Still missing
- No cis/trans phase data available
BP4 CSPEC BP4_Supporting requires REVEL score ≤ 0.15. The REVEL score for this variant is 0.58, which exceeds the threshold. SpliceAI max delta is 0.01, but this criterion is not applicable for BP4 on a missense variant per CSPEC guidance (BP4 SpliceAI rule is for non-canonical splicing and synonymous variants only). Details ▾Hide ▴
Evidence considered
- REVEL = 0.58 (> 0.15 BP4 threshold)
Sources
revel
BP5 No evidence that a pathogenic or likely pathogenic variant in an alternative monogenic diabetes gene has been identified in a proband carrying this variant. Details ▾Hide ▴
Still missing
- No alternate molecular diagnosis reported
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical splice sites, initiation codon, exon deletions). c.341G>A is a missense variant (p.Arg114His) and does not fall into any PVS1 null-variant bucket per the HNF1A CSPEC decision tree. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPPM6 is subsumed by PS2 per CSPEC v3.1.0 and is not applicable for this VCEP. No assumed de novo evidence was reviewed. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPPP2 is not applicable per CSPEC v3.1.0. The HNF1A gene constraint score (1.07) is not significant, and the CSPEC does not support using this criterion. Details ▾Hide ▴
Sources
PP5 VCEPPP5 is not applicable for this VCEP per CSPEC v3.1.0. The ClinGen Sequence Variant Interpretation VCEP Review Committee does not support use of this criterion. Details ▾Hide ▴
Sources
BP1 VCEPBP1 is not applicable per CSPEC v3.1.0. This criterion (missense variant in gene where primarily truncating variants cause disease) is not supported by the HNF1A CSPEC. Details ▾Hide ▴
Sources
BP3 VCEPNot applicable: variant is a substitution, not an in-frame deletion/insertion in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPBP6 is not applicable for this VCEP per CSPEC v3.1.0. The ClinGen Sequence Variant Interpretation VCEP Review Committee does not support use of this criterion. Details ▾Hide ▴
Sources
BP7 N/ABP7 applies to synonymous variants with SpliceAI delta < 0.2 and phyloP < 2.0. This variant is a missense substitution (c.341G>A, p.Arg114His), not a synonymous variant, and is therefore not eligible for BP7. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not a criterion in the standard ACMG/AMP 2015 framework nor in the ClinGen Monogenic Diabetes CSPEC for HNF1A. No applicable rule exists. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- HNF1A
- Transcript
- NM_000545.6
- Coding (HGVS c.)
- NM_000545.6:c.341G>A
- Protein (HGVS p.)
- NP_000536.5:p.(Arg114His)
- GRCh38
- chr12:120988847 G>A
- GRCh37
- chr12:121426650 G>A
- ClinVar
- 134508
- COSMIC
- COSV57459115
Gene diagram
Every interpreted variant in HNF1A, mapped onto the exon structure of NM_000545.6. Select a row to find it on the plot.
HNF1ANM_000545.6
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 HNF1A
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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
78 / 1,614,100 alleles
AF 4.83e-05 · 0 homozygotes · FAF 4.43e-05
gnomAD v2.1
14 / 282,682 alleles
AF 4.95e-05 · 0 homozygotes · FAF 9.37e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 4.8e-05 · 78 / 1,614,100 alleles · 0 hom · FAF 4.4e-05
| African/African American6 / 74,930 | 8e-05 |
| European (non-Finnish)65 / 1,180,056 | 5.5e-05 |
| Remaining individuals3 / 62,484 | 4.8e-05 |
| East Asian2 / 44,892 | 4.5e-05 |
| Admixed American2 / 60,006 | 3.3e-05 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 5e-05 · 14 / 282,682 alleles · 0 hom · FAF 9.4e-05
| African/African American4 / 24,950 | 0.00016 |
| Remaining individuals1 / 7,220 | 0.00014 |
| Admixed American2 / 35,422 | 5.6e-05 |
| European (non-Finnish)7 / 129,070 | 5.4e-05 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.83241e-05; MAF= 0.00483%, 78/1614100 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.00747e-05; MAF= 0.00801%, 6/74930 alleles, homozygotes = 0); grpmax FAF= 4.428e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95256e-05; MAF= 0.00495%, 14/282682 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160321; MAF= 0.01603%, 4/24950 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.580
- BayesDel
- 0.007
How the predictions were used
PP3 CSPEC PP3_Supporting requires REVEL score ≥ 0.70. The REVEL score for this variant is 0.58, which is below the threshold. SpliceAI max delta is 0.01, indicating no predicted splicing impact. BayesDel score is 0.007 (low). In silico tools do not support a deleterious prediction. Details ▾Hide ▴
Evidence considered
- REVEL = 0.58 (< 0.70 threshold)
- BayesDel = 0.007
- SpliceAI max delta = 0.01
Sources
BP4 CSPEC BP4_Supporting requires REVEL score ≤ 0.15. The REVEL score for this variant is 0.58, which exceeds the threshold. SpliceAI max delta is 0.01, but this criterion is not applicable for BP4 on a missense variant per CSPEC guidance (BP4 SpliceAI rule is for non-canonical splicing and synonymous variants only). Details ▾Hide ▴
Evidence considered
- REVEL = 0.58 (> 0.15 BP4 threshold)
Sources
revel
BP7 N/ABP7 applies to synonymous variants with SpliceAI delta < 0.2 and phyloP < 2.0. This variant is a missense substitution (c.341G>A, p.Arg114His), not a synonymous variant, and is therefore not eligible for BP7. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.58. BayesDel score = 0.00692358.
9 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 27899486 ↗Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population.Najmi LA et al. · 2017 FebNajmi et al. (2017) functionally characterized p.Arg114His (c.341G>A) among 27 rare HNF1A variants. In a luciferase reporter assay in HeLa cells, the variant demonstrated 83% transactivation activity compared to wild-type and 81% nuclear localization. It was classified as bioinformatically unlikely pathogenic (1/5 tools) and did not reduce transactivation below the 60% diabetes risk threshold. The variant was identified in 1 individual with diabetes and 1 control in the study cohorts.→ BS3 Names this variant
Source detail
c.341G>A R114H 83 — 81 Uncertain MODY/NA NA MODY (74, 75) Tol Ben C0 Polymorphism 22,9 3.318 × 10^-5 — Unlikely pathogenic (1/5) Class 3
Location Table 1; Results section 'Functional Evaluation'; Supplementary Table 1
Context Luciferase reporter assay (pGL3-RA rat albumin promoter) and immunofluorescence nuclear localization in transiently transfected HeLa cells
Other 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.ACMG/AMP standards and guidelines for sequence variant interpretation. This foundational methods paper does not discuss any specific HNF1A variants.Does not name this variant
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PMID 38093550 ↗An alternative approach using hs-CRP levels and age of onset in diagnostics of HNF1A-MODY.Kickova T et al. · 2024Study of hs-CRP-based screening for HNF1A-MODY in a diabetic cohort. The abstract describes HNF1A gene analysis in 50 participants but does not report specific variants including c.341G>A.Does not name this variant
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PMID 20301750 ↗WFS1 Spectrum Disorder.Adam MP et al. · 1993GeneReviews article on WFS1 Spectrum Disorder (wolframin). This paper discusses a different gene and does not pertain to HNF1A or this variant.Does not name this variant
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PMID 22962670 ↗Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline.Berglund L et al. · 2012Endocrine Society clinical practice guideline on evaluation and treatment of hypertriglyceridemia. No HNF1A variant data are discussed in this paper.Does not name this variant
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PMID 23771925 ↗Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth.Pihoker C et al. · 2013SEARCH for Diabetes in Youth study examining prevalence of MODY mutations (HNF1A, HNF4A, GCK) in a diverse US pediatric diabetes cohort. The specific variant NM_000545.6:c.341G>A was not identified in this paper.Does not name this variant
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PMID 24728327 ↗Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.Bodian DL et al. · 2014Study of germline variation in cancer-susceptibility genes in a healthy ancestrally diverse cohort. HNF1A variant c.341G>A was not specifically reported in this paper.Does not name this variant
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PMID 29792621 ↗Maturity-Onset Diabetes of the Young Overview.Adam MP et al. · 1993GeneReviews overview of Maturity-Onset Diabetes of the Young. General review of MODY genes and clinical features. The specific variant c.341G>A is not discussed.Does not name this variant
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PMID 23492873 ↗Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group et al. · 2013EGAPP Working Group recommendations on genomic profiling for type 2 diabetes risk assessment. General policy document; does not discuss specific HNF1A variants.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
78 / 1,614,100 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
5 Uncertain significance · 1 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB 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/467903868
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/134508/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/12-121426650-G-A?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr12-120988847-G-A?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/12-120988847-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000545.6%3Ac.341G…
- OncoKB ↗www.oncokb.org/gene/HNF1A/R114H
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=195619563
- 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= 4.83241e-05; MAF= 0.00483%, 78/1614100 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 8.00747e-05; MAF= 0.00801%, 6/74930 alleles, homozygotes = 0); grpmax FAF= 4.428e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.95256e-05; MAF= 0.00495%, 14/282682 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000160321; MAF= 0.01603%, 4/24950 alleles, homozygotes = 0); grpmax FAF= 9.374e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 134508)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.58. BayesDel score = 0.00692358.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57459115, n = 10 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.