About FGFR1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FGFR1 c.1368G>T, p.(Met456Ile)
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 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is present in gnomAD at low frequency — v2.1 AF 0.041% (115/280,958 alleles) and v4.1 AF 0.056% (905/1,614,218 alleles), both below the 0.1% threshold for PM2. However, the substantial carrier count (905 in v4.1) substantially weakens the evidence weight and this criterion should be considered borderline in the context of a rare disease gene.
Benign criteria applied · 1
BP6Supporting
BP6 · supporting
Ten of eleven clinical laboratory submissions in ClinVar classify NM_023110.3:c.1368G>T as Likely benign (7 labs) or Benign (3 labs), with only one VUS. While no expert panel review is available, the strong inter-laboratory consensus towards benign supports BP6 at the supporting level.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP6 supporting; combination = 1 supporting + 1 supporting benign, 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
905 / 1,614,218 alleles
gnomAD v4.1: 905 / 1,614,218 alleles. Recorded AF 0.000560643. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000409314; MAF= 0.04093%, 115/280958 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000784661; MAF= 0.07847%, 101/128718 alleles, homozygotes = 0); grpmax FAF= 0.00068549.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
11 reported laboratory submissions
7 Likely benign · 3 Benign · 1 Uncertain significance. ClinVar API review status: criteria provided, conflicting classifications.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FGFR1, a receptor tyrosine kinase, is altered by mutation, chromosomal rearrangement or amplification in various cancer types including lung and breas
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 Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 22 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_023110.3:c.1368G>T (p.Met456Ile) is a missense variant in exon 10 of FGFR1, encoding the tyrosine kinase domain.
This variant is present in gnomAD v2.1 at an allele frequency of 0.041% (115/280,958 alleles, 0 homozygotes) and in v4.1 at 0.056% (905/1,614,218 alleles, 0 homozygotes), with a grpmax filtering allele frequency of 0.069%. While below the formal BS1 threshold of 0.3%, the substantial carrier count in population databases (905 in v4.1) indicates this variant is not a rare private mutation.
In ClinVar, 10 of 11 clinical laboratory submissions classify this variant as Likely benign (7) or Benign (3), with one VUS. No submitter classifies the variant as pathogenic or likely pathogenic. The review status is 'criteria provided, single submitter' without expert panel consensus.
In silico predictions are discordant: REVEL (0.802) predicts damaging, while BayesDel (0.069) and SpliceAI (max delta 0.00) predict benign/no splicing impact. No variant-specific functional studies or case-level observations of pathogenicity were identified in the reviewed literature.
Applying generic ACMG/AMP 2015 combination rules: one supporting benign criterion (BP6) is met. PM2 is met at supporting level for pathogenicity but is substantially weakened by the high carrier count (905 in v4.1). The overall evidence profile favors a likely benign interpretation based on population frequency and multi-laboratory clinical consensus, though the formal BS1 threshold is not crossed.
No criteria match.
Met · 2
PM2 SupportingThe variant is present in gnomAD at low frequency — v2.1 AF 0.041% (115/280,958 alleles) and v4.1 AF 0.056% (905/1,614,218 alleles), both below the 0.1% threshold for PM2. However, the substantial carrier count (905 in v4.1) substantially weakens the evidence weight and this criterion should be considered borderline in the context of a rare disease gene. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.041% (115/280
- 958)
- v4.1 AF=0.056% (905/1
- 614
- 218)
- grpmax FAF=0.069%.
Still missing
- 905 carriers in v4.1 makes this a borderline PM2
- frequency may be too high for a rare disease gene.
Sources
BP6 SupportingTen of eleven clinical laboratory submissions in ClinVar classify NM_023110.3:c.1368G>T as Likely benign (7 labs) or Benign (3 labs), with only one VUS. While no expert panel review is available, the strong inter-laboratory consensus towards benign supports BP6 at the supporting level. Details ▾Hide ▴
Evidence considered
- ClinVar: 7 Likely benign
- 3 Benign
- 1 VUS. Majority consensus supports benign classification.
Still missing
- No expert panel review
- BP6 applied at supporting based on multi-laboratory clinical consensus.
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No ClinVar or literature evidence identifies a different nucleotide change at the same codon (c.1368) producing the same amino acid change (p.Met456Ile). PS1 requires a known pathogenic variant at the same position with a different nucleotide substitution. Details ▾Hide ▴
Evidence considered
- No same-amino-acid comparator variant identified at codon 456.
Sources
clinvar ↗pm5_candidates
PS2 No de novo observation data are available for this variant. ClinVar submissions do not report de novo status, and no reviewed publication documents a confirmed de novo occurrence of NM_023110.3:c.1368G>T. Details ▾Hide ▴
Evidence considered
- No de novo data identified in ClinVar submissions or reviewed literature.
Still missing
- No proband-level segregation or parent-of-origin data available.
Sources
PS3 No well-established in vitro or in vivo functional studies have been identified for p.Met456Ile. OncoKB classifies this variant as 'Unknown Oncogenic Effect' with no variant-specific functional evidence. No reviewed publication reports experimental functional data for this variant. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional studies found in literature.
Still missing
- No functional data available for this specific variant.
Sources
PS4 No case-control study or systematic phenotypic data are available to demonstrate significantly increased prevalence of this variant in affected individuals versus controls. The variant is observed in 115–905 population alleles in gnomAD, inconsistent with a highly penetrant rare disease variant. Details ▾Hide ▴
Evidence considered
- Variant absent from case-control data
- gnomAD carrier count (115–905) is inconsistent with a rare fully penetrant pathogenic variant.
Still missing
- No case-control or cohort enrichment data.
Sources
PM1 Although p.Met456Ile resides in the tyrosine kinase domain of FGFR1, the variant is not located in a statistically significant mutational hotspot per the hotspot screen. Without CSPEC/VCEP guidance identifying codon 456 as a critical functional domain for PM1, this criterion cannot be applied. Details ▾Hide ▴
Evidence considered
- Hotspot analysis: not in a statistically significant hotspot
- no CSPEC domain-level guidance for FGFR1.
PM5 Automated PM5 candidate harvesting found no same-residue (Met456) comparator variants with pathogenic or likely pathogenic classification in ClinVar. No manual comparator candidates were identified. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue candidates
- unable to assess PM5.
Sources
pm5_candidatesclinvar ↗
PM6 No de novo observation with unconfirmed parentage has been reported for this variant. No ClinVar submission or reviewed publication documents a de novo event. Details ▾Hide ▴
PP1 No family segregation data are available for NM_023110.3:c.1368G>T. No reviewed publication reports cosegregation of this variant with disease in affected family members. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family-based segregation analysis for this variant.
PP2 FGFR1 has a mix of pathogenic and benign missense variants; it does not exhibit a low rate of benign missense variation that would support PP2. Without CSPEC/VCEP guidance defining a missense constraint metric for FGFR1, PP2 cannot be applied. Details ▾Hide ▴
Evidence considered
- gnomAD shows numerous FGFR1 missense variants at measurable frequencies
- gene not constrained for missense variation.
Sources
PP3 In silico predictions are discordant: REVEL score 0.802 suggests a damaging effect, but BayesDel score 0.069 predicts benign and SpliceAI delta 0.00 predicts no splicing impact. A single damaging prediction (REVEL) does not meet the 'multiple lines of computational evidence' threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL=0.802 (damaging)
- BayesDel=0.069 (benign)
- SpliceAI=0.00 (neutral). Only 1/3 tools support pathogenicity.
Sources
PP4 No patient phenotype information is available in the case data. PP4 requires that the patient's phenotype or family history is highly specific for a disease associated with FGFR1, which cannot be assessed. Details ▾Hide ▴
Evidence considered
- No proband phenotype data provided.
Still missing
- Proband phenotype not available.
PP5 ClinVar reports a consensus classification of Likely benign/Benign from 10 of 11 clinical laboratories, with only 1 VUS. No reputable source classifies this variant as pathogenic. The ClinVar review status is 'criteria provided, single submitter' with no expert panel review. Details ▾Hide ▴
Evidence considered
- ClinVar: 7 LB
- 3 B
- 1 VUS
- no submitter classifies as P/LP
- no expert panel review.
Sources
BA1 The maximum allele frequency in gnomAD is 0.056% (v4.1) with grpmax FAF of 0.069%, well below the 1% threshold required for BA1. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.041%
- v4.1 AF=0.056%
- grpmax FAF=0.069%. All well below 1%.
Sources
BS1 The maximum allele frequency in gnomAD is 0.056% (v4.1) with grpmax FAF of 0.069%, below the 0.3% threshold for BS1. While the variant has 905 carriers in v4.1, the frequency does not formally exceed the BS1 cutoff of >0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD max AF=0.056%
- grpmax FAF=0.069%. Below BS1 threshold of 0.3%.
Still missing
- 905 carriers in v4.1 approaches but does not meet the formal BS1 threshold
- may warrant consideration in final classification.
Sources
BS2 No homozygous individuals are observed in gnomAD (v2.1 or v4.1). BS2 requires observation in a homozygous state in a healthy adult, which is not supported by available data. Details ▾Hide ▴
BS3 No well-established in vitro or in vivo functional studies demonstrate that p.Met456Ile has no deleterious effect. OncoKB lists the variant as 'Unknown Oncogenic Effect' with no functional data. Details ▾Hide ▴
Evidence considered
- No functional studies evaluating p.Met456Ile effect identified.
Still missing
- No functional characterization of this variant.
Sources
BS4 No family segregation data are available to demonstrate lack of cosegregation with disease in affected family members. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No family-based segregation analysis.
BP1 FGFR1-related disorders are not solely caused by loss-of-function truncating variants; activating missense variants in the tyrosine kinase domain are a well-established pathogenic mechanism (e.g., craniosynostosis, Hartsfield syndrome, osteoglophonic dysplasia). BP1 requires that the disease mechanism is exclusively truncating, which is not the case for FGFR1. Details ▾Hide ▴
Evidence considered
- FGFR1 disease mechanism includes gain-of-function and dominant-negative missense variants
- not solely LOF.
Sources
pvs1_gene_context
BP2 No data are available regarding observation of this variant in trans with a known pathogenic dominant FGFR1 variant. Details ▾Hide ▴
Evidence considered
- No phase data available.
BP4 In silico predictions are discordant: REVEL 0.802 predicts damaging, while BayesDel 0.069 and SpliceAI 0.00 predict benign/neutral. BP4 requires multiple lines of computational evidence suggesting no impact, which is not met given the REVEL score in the damaging range. Details ▾Hide ▴
Evidence considered
- REVEL=0.802 (damaging)
- BayesDel=0.069 (benign)
- SpliceAI=0.00 (neutral). Discordant
- REVEL prevents BP4.
Sources
BP5 No data are available indicating that this variant has been observed in a case with an alternative molecular cause for disease. Details ▾Hide ▴
Evidence considered
- No alternative molecular cause data available.
PS5 No ClinGen-recognized expert panel or authoritative clinical practice guideline has classified NM_023110.3:c.1368G>T as pathogenic. Available ClinVar classifications are from single submitters without expert panel review. Details ▾Hide ▴
Evidence considered
- No expert panel classification
- ClinVar review status is 'criteria provided
- single submitter.'
Still missing
- No expert panel or authoritative guideline classification.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_023110.3:c.1368G>T is a missense variant (p.Met456Ile) in exon 10 and does not fall into any generic PVS1 null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). The PVS1 variant assessment confirms apply_generic_pvs1_framework is false. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not a null variant eligible for PVS1.
Sources
pvs1_variant_assessmentpvs1_gene_context
PM3 N/APM3 applies to recessive disorders with a pathogenic variant in trans; no recessive inheritance model or trans data are provided for this case. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to non-frameshift indels altering protein length; this is a single-nucleotide missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ABP3 applies to in-frame indels in repetitive regions; this is a single-nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_023110.3:c.1368G>T is a missense variant (p.Met456Ile), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 not applicable.
Identifiers
- Gene
- FGFR1
- Transcript
- NM_023110.3
- Coding (HGVS c.)
- NM_023110.3:c.1368G>T
- Protein (HGVS p.)
- NP_075598.2:p.(Met456Ile)
- GRCh38
- chr8:38418290 C>A
- GRCh37
- chr8:38275808 C>A
- ClinVar
- 362896
Gene diagram
Every interpreted variant in FGFR1, mapped onto the exon structure of NM_023110.3. Select a row to find it on the plot.
FGFR1NM_023110.3
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 FGFR1
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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
905 / 1,614,218 alleles
AF 0.000561 · 0 homozygotes · FAF 0.000679
gnomAD v2.1
115 / 280,958 alleles
AF 0.000409 · 0 homozygotes · FAF 0.000685
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00056 · 905 / 1,614,218 alleles · 0 hom · FAF 0.00068
| European (non-Finnish)849 / 1,180,042 | 0.00072 |
| Middle Eastern3 / 6,062 | 0.00049 |
| Admixed American20 / 60,026 | 0.00033 |
| Remaining individuals19 / 62,512 | 0.0003 |
| European (Finnish)6 / 64,018 | 9.4e-05 |
| African/African American4 / 75,066 | 5.3e-05 |
| South Asian4 / 91,090 | 4.4e-05 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00041 · 115 / 280,958 alleles · 0 hom · FAF 0.00069
| European (non-Finnish)101 / 128,718 | 0.00078 |
| Remaining individuals4 / 7,150 | 0.00056 |
| Admixed American7 / 35,374 | 0.0002 |
| African/African American1 / 24,198 | 4.1e-05 |
| European (Finnish)1 / 25,018 | 4e-05 |
| South Asian1 / 30,602 | 3.3e-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= 0.000560643; MAF= 0.05606%, 905/1614218 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000719466; MAF= 0.07195%, 849/1180042 alleles, homozygotes = 0); grpmax FAF= 0.00067933.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000409314; MAF= 0.04093%, 115/280958 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000784661; MAF= 0.07847%, 101/128718 alleles, homozygotes = 0); grpmax FAF= 0.00068549.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.802
- BayesDel
- 0.069
How the predictions were used
PP3 In silico predictions are discordant: REVEL score 0.802 suggests a damaging effect, but BayesDel score 0.069 predicts benign and SpliceAI delta 0.00 predicts no splicing impact. A single damaging prediction (REVEL) does not meet the 'multiple lines of computational evidence' threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL=0.802 (damaging)
- BayesDel=0.069 (benign)
- SpliceAI=0.00 (neutral). Only 1/3 tools support pathogenicity.
Sources
BP4 In silico predictions are discordant: REVEL 0.802 predicts damaging, while BayesDel 0.069 and SpliceAI 0.00 predict benign/neutral. BP4 requires multiple lines of computational evidence suggesting no impact, which is not met given the REVEL score in the damaging range. Details ▾Hide ▴
Evidence considered
- REVEL=0.802 (damaging)
- BayesDel=0.069 (benign)
- SpliceAI=0.00 (neutral). Discordant
- REVEL prevents BP4.
Sources
BP7 N/ANM_023110.3:c.1368G>T is a missense variant (p.Met456Ile), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 not applicable.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.802. BayesDel score = 0.0686773.
7 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
-
PMID 21082653 ↗Genetic basis of potential therapeutic strategies for craniosynostosis.Melville H et al. · 2010Review of genetic basis of craniosynostosis and potential therapeutic strategies. Discusses FGFR1 in the context of craniosynostosis syndromes at the gene level. NM_023110.3:c.1368G>T was not specifically mentioned in the abstract.Does not name this variant
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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. · 2015ACMG/AMP 2015 standards and guidelines for interpretation of sequence variants. A generic methodology paper that does not discuss NM_023110.3:c.1368G>T or any specific FGFR1 variant.Does not name this variant
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PMID 31275557 ↗Pan-cancer repository of validated natural and cryptic mRNA splicing mutations.Shirley BC et al. · 2018Pan-cancer repository of validated natural and cryptic mRNA splicing mutations, describing an information theory-based approach to identify splice-altering variants in TCGA and ICGC tumor genomes. NM_023110.3:c.1368G>T was not identified in this resource.Does not name this variant
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PMID 20301628 ↗FGFR Craniosynostosis Syndromes Overview.Adam MP et al. · 1993GeneReviews overview of FGFR craniosynostosis syndromes. Discusses FGFR1-related craniosynostosis at the gene level. NM_023110.3:c.1368G>T was not identified in the available abstract.Does not name this variant
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PMID 35099867 ↗Encephalocraniocutaneous Lipomatosis.Adam MP et al. · 1993GeneReviews overview of encephalocraniocutaneous lipomatosis. FGFR1 is discussed at the gene level. NM_023110.3:c.1368G>T was not identified in the available abstract.Does not name this variant
-
PMID 38648328 ↗Osteoglophonic Dysplasia.Adam MP et al. · 1993GeneReviews overview of osteoglophonic dysplasia, an FGFR1-related skeletal disorder. NM_023110.3:c.1368G>T was not identified in the available abstract.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. A variant classification framework paper; does not discuss NM_023110.3:c.1368G>T.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
905 / 1,614,218 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
7 Likely benign · 3 Benign · 1 Uncertain significance
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/362896/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-38275808-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-38418290-C-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-38418290-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_023110.3%3Ac.1368…
- OncoKB ↗www.oncokb.org/gene/FGFR1/M456I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=FGFR1+c.1368G%3ET
- 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= 0.000560643; MAF= 0.05606%, 905/1614218 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000719466; MAF= 0.07195%, 849/1180042 alleles, homozygotes = 0); grpmax FAF= 0.00067933.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000409314; MAF= 0.04093%, 115/280958 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000784661; MAF= 0.07847%, 101/128718 alleles, homozygotes = 0); grpmax FAF= 0.00068549.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00043426338074041906, 8/18422 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Benign (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 362896)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.802. BayesDel score = 0.0686773.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FGFR1, a receptor tyrosine kinase, is altered by mutation, chromosomal rearrangement or amplification in various cancer types including lung and breas
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.