About FBXW7
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FBXW7 c.1436G>T, p.(Arg479Leu)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic 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 Not recorded. 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PS3Moderate
PS3 · moderate
The R479L substitution was directly tested in a co-immunoprecipitation assay in 293T cells and demonstrated complete loss of FBXW7 interaction with its substrate DAB2IP, confirming disruption of substrate recognition function. This is a single study with direct variant testing using an indirect reporter-type assay, supporting moderate strength.
PM1Moderate
PM1 · moderate
The variant is located at residue Arg479 within the WD40 substrate recognition domain of FBXW7, a well-characterized critical functional domain. This residue is a statistically significant mutational hotspot per cancerhotspots.org. Functional studies (PMID:24912918, PMID:17646408, PMID:17646409) confirm that mutations at this position disrupt FBXW7 substrate binding. The variant lies in the WD40 repeat domain that mediates substrate recognition, and no benign variation is observed at this position in population databases.
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0. Allele frequency is below the 0.1% PM2 threshold for rare variant support in the generic ACMG framework.
PP3Supporting
PP3 · supporting
Multiple lines of computational evidence support a deleterious effect: REVEL score of 0.583 (above the 0.5 threshold for pathogenicity) and SpliceAI predicts a possible splice alteration with a max delta score of 0.33 (acceptor loss). The variant also lies at a statistically significant mutational hotspot. BayesDel score is low at 0.125 but does not outweigh the preponderance of evidence from REVEL and SpliceAI.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 moderate, PM1 moderate, PM2 supporting, PP3 supporting; combination = 2 moderate + 2 supporting, which maps to Likely Pathogenic.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.330 maximum delta
Recorded SpliceAI maximum delta score: 0.330. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded. ClinVar API review status: criteria provided, single submitter.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
18 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV55899054, n = 18 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 4 met · 20 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_033632.3:c.1436G>T (p.Arg479Leu) is a missense variant in exon 10 of FBXW7, located at residue 479 within the WD40 substrate recognition domain.
This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting PM2 at supporting strength.
The variant lies at a statistically significant mutational hotspot (cancerhotspots.org) within the WD40 domain, a well-characterized functional domain critical for FBXW7 substrate recognition. Mutations at residue 479 have been shown to disrupt FBXW7-substrate interactions across multiple studies, meeting PM1 at moderate strength.
Functional studies directly testing the R479L substitution in a co-immunoprecipitation assay (293T cells) demonstrated complete loss of FBXW7 interaction with its substrate DAB2IP, confirming disruption of substrate recognition function. This meets PS3 at moderate strength.
Multiple in silico tools support a deleterious effect: REVEL score 0.583 and SpliceAI max delta score 0.33 (acceptor loss prediction). This meets PP3 at supporting strength.
The variant has been reported in ClinVar (Variation ID: 4530538) as Tier I - Strong with a single submitter (1-star review status). It has been observed in somatic cancers (COSMIC COSV55899054, 18 counts) but lacks independent germline proband observations. These data are insufficient for PP5 or PS4.
No criteria match.
Met · 4
PS3 ModerateThe R479L substitution was directly tested in a co-immunoprecipitation assay in 293T cells and demonstrated complete loss of FBXW7 interaction with its substrate DAB2IP, confirming disruption of substrate recognition function. This is a single study with direct variant testing using an indirect reporter-type assay, supporting moderate strength. Details ▾Hide ▴
Evidence considered
- PMID:24912918: 293T co-immunoprecipitation assay showing R479L abolishes FBXW7-DAB2IP interaction
- confirming loss of substrate recognition.
Still missing
- Single study
- additional independent functional replication would strengthen the evidence to strong.
Sources
PM1 ModerateThe variant is located at residue Arg479 within the WD40 substrate recognition domain of FBXW7, a well-characterized critical functional domain. This residue is a statistically significant mutational hotspot per cancerhotspots.org. Functional studies (PMID:24912918, PMID:17646408, PMID:17646409) confirm that mutations at this position disrupt FBXW7 substrate binding. The variant lies in the WD40 repeat domain that mediates substrate recognition, and no benign variation is observed at this position in population databases. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: statistically significant mutational hotspot at residue 479.
- PMID:24912918: R479L disrupts FBXW7-DAB2IP interaction.
- PMID:17646408: R479Q mutation in T-ALL disrupts FBXW7-NOTCH1 interaction.
- PMID:17646409: R479Q mutation in T-ALL disrupts FBXW7 substrate binding.
- gnomAD: absent from population databases
- supporting no benign variation at this position.
Sources
PM2 SupportingThis variant is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0. Allele frequency is below the 0.1% PM2 threshold for rare variant support in the generic ACMG framework. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1.
- Absent from gnomAD v4.1.
- Absent from gnomAD-Canada v1.0.
Still missing
- Coverage at this position should be verified across gnomAD datasets.
Sources
PP3 SupportingMultiple lines of computational evidence support a deleterious effect: REVEL score of 0.583 (above the 0.5 threshold for pathogenicity) and SpliceAI predicts a possible splice alteration with a max delta score of 0.33 (acceptor loss). The variant also lies at a statistically significant mutational hotspot. BayesDel score is low at 0.125 but does not outweigh the preponderance of evidence from REVEL and SpliceAI. Details ▾Hide ▴
Evidence considered
- REVEL: 0.583 (deleterious
- above 0.5 threshold).
- SpliceAI: max delta 0.33 (acceptor loss Δ = 0.33
- above 0.2 threshold).
- BayesDel: 0.125 (low
- but does not outweigh REVEL and SpliceAI).
- Hotspot: residue 479 is a statistically significant mutational hotspot.
Still missing
- BayesDel score is discordant
- dominant model may explain differing calibration.
Sources
Not met · 20 · evaluated, threshold not reached
PS1 PS1 requires a different nucleotide change at the same codon producing the same amino acid change (p.Arg479Leu) that has been established as pathogenic. No alternative nucleotide change at c.1436 producing p.Arg479Leu was identified in ClinVar or the reviewed literature. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change producing p.Arg479Leu was identified.
PS2 PS2 requires a de novo observation with confirmed maternity and paternity. No de novo data for NM_033632.3:c.1436G>T was identified in ClinVar submissions, the reviewed literature, or any other source. Details ▾Hide ▴
Evidence considered
- No de novo observation was identified in any reviewed source.
PS4 PS4 requires statistically significant enrichment in affected individuals or a substantial number of independent proband observations. This variant has been observed in COSMIC (18 somatic counts, COSV55899054) but these are somatic cancer observations. No independent germline proband count is available; ClinVar submissions could not be extracted (0 submissions parsed), and the reviewed literature did not identify any germline probands with this variant. PMID:25768946 (rhabdomyosarcoma genomics) was screened but the variant was not identified in the full text. Details ▾Hide ▴
Evidence considered
- COSMIC: 18 somatic observations (COSV55899054).
- ClinVar: Variation ID 4530538
- 0 submissions extracted
- no proband count available.
Still missing
- No germline proband observations available.
Sources
PM5 PM5 requires a different pathogenic missense variant at the same amino acid residue (Arg479). The automated PM5 candidate search identified 0 same-residue pathogenic comparator variants in ClinVar. While R479Q has been reported in the literature (PMID:17646408, PMID:17646409) as a functionally damaging T-ALL-associated mutation, it has not been classified as pathogenic in ClinVar, and functional data from a sister variant does not independently satisfy PM5 without a clinical classification. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue ClinVar candidates.
- R479Q reported in literature (PMID:17646408
- PMID:17646409) but no ClinVar pathogenic classification.
Still missing
- R479Q has functional evidence but lacks ClinVar classification
- a submitter could classify R479Q to enable PM5 application.
Sources
pm5_candidates
PM6 PM6 requires a de novo observation with confirmed maternity and paternity. No de novo data was identified for this variant in any reviewed source. Details ▾Hide ▴
Evidence considered
- No de novo observation was identified.
PP1 PP1 requires cosegregation of the variant with disease in multiple affected family members. No segregation data was available for this variant in ClinVar submissions or the reviewed literature. Details ▾Hide ▴
Evidence considered
- No segregation data available.
PP2 PP2 applies when a gene has a low rate of benign missense variation and missense variants are a known disease mechanism. FBXW7 is a tumor suppressor with disease-associated missense variants in the WD40 domain; however, without a VCEP-specified z-score or missense constraint metric, PP2 cannot be automatically applied under the generic ACMG framework. Details ▾Hide ▴
Evidence considered
- FBXW7 missense variants are a known disease mechanism in the WD40 domain
- but no VCEP-specified constraint data is available for generic PP2 application.
Still missing
- FBXW7 missense constraint metrics (e.g.
- gnomAD missense Z-score) could support PP2 but are not formalized for generic ACMG.
PP4 PP4 requires the variant to be found in a patient with a phenotype highly specific for FBXW7-related disease. No patient-specific phenotype information was available for this variant. The ClinVar record lacks extractable submission details and no clinical phenotype data was identified in the reviewed literature. Details ▾Hide ▴
PP5 PP5 requires a reputable source (≥3-star ClinVar expert panel) to have classified the variant as pathogenic. The ClinVar record (Variation ID: 4530538) has a review status of 'criteria provided, single submitter' (1-star). The classification is 'Tier I - Strong,' which is a somatic AMP/ASCO/CAP tier, not an ACMG germline classification. Under the governing PP5 rule (≥3-star EP required), this does not meet the threshold for supporting strength. Submission details could not be extracted (0 submissions parsed). Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID: 4530538
- classification: Tier I - Strong (somatic tier system).
- Review status: criteria provided
- single submitter (1-star).
- 0 submissions extracted
- 0 expert panel submissions.
Still missing
- 3-star ClinVar EP classification would be required to apply PP5.
Sources
BA1 BA1 requires an allele frequency >1% in gnomAD. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- Absent from all gnomAD populations
- frequency is 0%.
Sources
BS1 BS1 requires an allele frequency >0.3% in gnomAD. This variant is absent from all gnomAD datasets. Details ▾Hide ▴
BS2 BS2 requires observation in a healthy adult at a frequency inconsistent with a fully penetrant disorder. The variant is absent from all population databases; no healthy adult observation exists. Details ▾Hide ▴
BS3 BS3 requires well-established functional studies showing no damaging effect. The only functional study of this variant (PMID:24912918) demonstrated loss of FBXW7-DAB2IP interaction, confirming a damaging loss-of-function effect. No benign functional data exists. Details ▾Hide ▴
Evidence considered
- PMID:24912918: functional data shows damaging effect (loss of substrate interaction)
- not benign.
Sources
BS4 BS4 requires lack of segregation in affected family members. No segregation data is available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available.
BP1 BP1 applies to missense variants in genes where only truncating variants cause disease. FBXW7-related neurodevelopmental syndrome and Wilms tumor predisposition are associated with both truncating and missense variants, particularly missense variants in the WD40 domain. Therefore BP1 does not apply. Details ▾Hide ▴
Evidence considered
- FBXW7 germline disease includes WD40-domain missense variants as a known mechanism.
BP2 BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder. No such observation exists. Details ▾Hide ▴
Evidence considered
- No trans observation available.
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. REVEL score (0.583) and SpliceAI (max delta 0.33) both predict a deleterious effect. While BayesDel (0.125) is low, the preponderance of in silico evidence does not support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.583: deleterious prediction.
- SpliceAI max delta 0.33: possible splice impact.
- BayesDel 0.125: discordant but does not outweigh the other tools.
Sources
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such evidence was identified. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis identified.
BP6 BP6 requires a reputable source (≥3-star ClinVar EP) to have classified the variant as benign. The ClinVar record classifies this variant as 'Tier I - Strong' (pathogenic), not benign. Additionally, the review status is 1-star, not the required 3-star threshold. Details ▾Hide ▴
Evidence considered
- ClinVar classification is pathogenic (Tier I - Strong)
- not benign.
- Review status: 1-star (criteria provided
- single submitter).
Sources
PS5 PS5 requires the same amino acid change (p.Arg479Leu) to have been established as pathogenic via a different nucleotide change at the same codon. No alternative nucleotide change at codon 479 producing p.Arg479Leu was identified in ClinVar or the reviewed literature. The ClinVar record (Variation ID: 4530538) lists the variant under NM_001349798.2:c.1436G>T, not an alternative nucleotide change. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change at codon 479 producing p.Arg479Leu was identified.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is restricted to null variants (nonsense, frameshift, canonical ±1,2 splice sites). NM_033632.3:c.1436G>T is a missense substitution (p.Arg479Leu) in exon 10 and does not fall into any PVS1 null-variant bucket per ClinGen SVI recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense variant
- not eligible for generic PVS1 null-variant framework.
Sources
PM3 N/APM3 applies to recessive disorders where the variant is found in trans with another pathogenic variant. FBXW7-associated disease is autosomal dominant; no trans-configuration data is relevant. Details ▾Hide ▴
Evidence considered
- Not applicable to dominant disorders.
PM4 N/APM4 applies to in-frame deletions/insertions or stop-loss variants causing protein length change. This is a missense substitution. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions; this is a missense substitution. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
BP7 N/ABP7 applies to synonymous variants predicted to have no splice impact. NM_033632.3:c.1436G>T is a missense variant (p.Arg479Leu), not a synonymous variant. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
Identifiers
- Gene
- FBXW7
- Transcript
- NM_033632.3
- Coding (HGVS c.)
- NM_033632.3:c.1436G>T
- Protein (HGVS p.)
- NP_361014.1:p.(Arg479Leu)
- GRCh38
- chr4:152326214 C>A
- GRCh37
- chr4:153247366 C>A
- ClinVar
- 4530538
- COSMIC
- COSV55899054
Gene diagram
Every interpreted variant in FBXW7, mapped onto the exon structure of NM_033632.3. Select a row to find it on the plot.
FBXW7NM_033632.3
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 FBXW7
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.583
- BayesDel
- 0.125
How the predictions were used
PP3 SupportingMultiple lines of computational evidence support a deleterious effect: REVEL score of 0.583 (above the 0.5 threshold for pathogenicity) and SpliceAI predicts a possible splice alteration with a max delta score of 0.33 (acceptor loss). The variant also lies at a statistically significant mutational hotspot. BayesDel score is low at 0.125 but does not outweigh the preponderance of evidence from REVEL and SpliceAI. Details ▾Hide ▴
Evidence considered
- REVEL: 0.583 (deleterious
- above 0.5 threshold).
- SpliceAI: max delta 0.33 (acceptor loss Δ = 0.33
- above 0.2 threshold).
- BayesDel: 0.125 (low
- but does not outweigh REVEL and SpliceAI).
- Hotspot: residue 479 is a statistically significant mutational hotspot.
Still missing
- BayesDel score is discordant
- dominant model may explain differing calibration.
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. REVEL score (0.583) and SpliceAI (max delta 0.33) both predict a deleterious effect. While BayesDel (0.125) is low, the preponderance of in silico evidence does not support a benign interpretation. Details ▾Hide ▴
Evidence considered
- REVEL 0.583: deleterious prediction.
- SpliceAI max delta 0.33: possible splice impact.
- BayesDel 0.125: discordant but does not outweigh the other tools.
Sources
BP7 N/ABP7 applies to synonymous variants predicted to have no splice impact. NM_033632.3:c.1436G>T is a missense variant (p.Arg479Leu), not a synonymous variant. Details ▾Hide ▴
Evidence considered
- Not applicable to missense variants.
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.33). REVEL score = 0.583. BayesDel score = 0.124658.
6 paper records listed. 3 cited in the classification.
Cited in the classification
-
PMID 17646408 ↗The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia.Thompson BJ et al. · 2007 Aug 6Reports FBW7 mutations in T-ALL cell lines and primary samples, identifying R465H, R479Q, and R505C as recurrent mutations in the WD40 domain that disrupt NOTCH1 binding. The variant R479L was not studied; the paper examined R479Q (c.1585G>A), a different amino acid substitution at the same codon.→ PM1 Does not name this variant
Source detail
we replaced the arginine at position 465, 479, or 505 with cysteine (DN FBW7 R465C and DN FBW7 R505C) or glutamine (DN FBW7 R479Q) and tested their abilities to interact with N1-IC
Location Results; Table of T-ALL mutations; Figure panels showing DN FBW7 mutants
Context Co-immunoprecipitation, T-ALL cell lines and 293T cells
-
PMID 17646409 ↗FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors.O'Neil J et al. · 2007 Aug 6Reports that FBW7 mutations in T-ALL cell lines (including R465H, R479Q, and R505C) mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. The R479Q mutant showed defective NOTCH binding with modest residual interaction. The variant R479L was not studied.→ PM1 Does not name this variant
Source detail
the mutants were defective in NOTCH binding, although FBW7R479Q showed a modest amount of residual binding
Location Results, Figure 6A
Context Co-immunoprecipitation, T-ALL cell lines
-
PMID 24912918 ↗Negative regulation of DAB2IP by Akt and SCFFbw7 pathways.Dai X et al. · 2014 May 30Three T-ALL-associated mutations in FBXW7 (R465H, R479L, R505C) were tested in a co-immunoprecipitation assay and shown to abolish interaction with the substrate DAB2IP, confirming loss of substrate recognition function.→ PS3 → PM1 Names this variant
Source detail
Consistent with DAB2IP being a substrate of Fbw7, we found that three T-ALL associated mutations in Fbw7 (R465H, R479L, and R505C) no longer interacted of Fbw7 with DAB2IP (Figure 4B), providing further evidence that DAB2IP interaction with Fbw7 is through the substrate recognition domain of Fbw7.
Location Results, Figure 4B
Context Co-immunoprecipitation assay, 293T cells, FLAG-DAB2IP and HA-FBW7 constructs
Other recorded publications
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PMID 22608923 ↗Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase.Min SH et al. · 2012Discusses the regulation of FBXW7 stability and tumor suppressor function by the Pin1 prolyl isomerase. Reports that FBXW7 is a tumor suppressor frequently mutated in human cancers, but does not identify or test any specific FBXW7 missense variants including R479L.Does not name this variant
-
PMID 25768946 ↗Clonality and evolutionary history of rhabdomyosarcoma.Chen L et al. · 2015Whole-genome sequencing study of 44 rhabdomyosarcoma tumor-normal pairs to infer subclonality and evolutionary history. Reports FBXW7 among genes with somatic alterations in rhabdomyosarcoma but does not identify the specific variant NM_033632.3:c.1436G>T or p.Arg479Leu.Does not name this variant
-
PMID 27993330 ↗Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists.AMP/ASCO/CAP joint consensus guideline for the interpretation of sequence variants in cancer. Provides standards for somatic variant tier classification but does not discuss any specific FBXW7 variants or the variant under assessment.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.330
Open source ↗
ClinVar
Captured ClinVar source record
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/4530538/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/4-153247366-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr4-152326214-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/4-152326214-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_033632.3%3Ac.1436…
- OncoKB ↗www.oncokb.org/gene/FBXW7/R479L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=210669360
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar but submission details could not be extracted. (ClinVarID = 4530538)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.33). REVEL score = 0.583. BayesDel score = 0.124658.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55899054, n = 18 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.