FGFR1c.521C>GUncertain significance

Print report

Variant interpretation report

FGFR1 c.521C>G, p.(Thr174Arg)

NM_001174067.1:c.521C>G NP_001167538.1:p.(Thr174Arg) View identifiers

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.

About FGFR1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 supporting (benign) · 1 supporting (pathogenic)
Expert rules: Not recorded
Other laboratories (ClinVar): 2 Uncertain significance
Pipeline record: 4 Jul 2026 · version 7.0.1

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): This variant is present at very low frequency in population databases. gnomAD v2.1 allele frequency is 0.0097% (27/278,536 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.03% (483/1,614,016 alleles, 0 homozygotes), both below the 0.1% threshold for PM2_supporting. Absent from gnomAD-Canada v1.0.
BP4 (supporting): Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.263 (below the typical pathogenic threshold), BayesDel score is −0.147 (negative, consistent with benign), and SpliceAI predicts no splicing impact (max delta 0.01). All three independent in silico predictors converge on a benign or neutral prediction.

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

This variant is present at very low frequency in population databases. gnomAD v2.1 allele frequency is 0.0097% (27/278,536 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.03% (483/1,614,016 alleles, 0 homozygotes), both below the 0.1% threshold for PM2_supporting. Absent from gnomAD-Canada v1.0.

Benign criteria applied · 1

BP4Supporting

BP4 · supporting

Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.263 (below the typical pathogenic threshold), BayesDel score is −0.147 (negative, consistent with benign), and SpliceAI predicts no splicing impact (max delta 0.01). All three independent in silico predictors converge on a benign or neutral prediction.

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, BP4 supporting benign; 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

483 / 1,614,016 alleles

gnomAD v4.1: 483 / 1,614,016 alleles. Recorded AF 0.000299254. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 9.69354e-05; MAF= 0.00969%, 27/278536 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000190027; MAF= 0.01900%, 24/126298 alleles, homozygotes = 0); grpmax FAF= 0.00011951.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0001085894233901618, 2/18418 alleles, homozygotes = 0).

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

2 Uncertain significance.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

2 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV58328267, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

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 · 19 not met · 2 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_001174067.1:c.521C>G (p.Thr174Arg) is a missense variant in exon 5 of FGFR1, encoding a substitution of threonine to arginine at codon 174 in the extracellular Ig-like domain.

This variant is present at very low frequency in population databases: gnomAD v2.1 (27/278,536 alleles, AF=0.0097%) and gnomAD v4.1 (483/1,614,016 alleles, AF=0.03%), meeting PM2 at the supporting level. It is absent from gnomAD-Canada v1.0.

Computational predictors unanimously suggest a benign or neutral effect: REVEL score is 0.263 (below the pathogenic threshold), BayesDel is −0.147 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.01), meeting BP4 at the supporting level.

OncoKB annotates this variant as Likely Neutral. COSMIC records this variant in two somatic cancer samples (COSV58328267), but no germline functional or case-level evidence of pathogenicity is available.

ClinVar classifies this variant as Uncertain significance (Variation ID: 1024176) based on three submissions, all with criteria provided at the single-submitter level. No expert panel has reviewed this variant.

A comprehensive functional screen of 160 FGFR variants (PMID:34272467) did not include Thr174Arg. No variant-specific functional studies have been performed.

FGFR1 variant classification literature (PMID:37805574) establishes domain-based enrichment for IHH-associated missense variants but does not specifically address the Thr174 residue.

With PM2_supporting and BP4_supporting both met, the evidence is balanced and insufficient to classify this variant as pathogenic or benign. The variant remains a Variant of Uncertain Significance (VUS) per ACMG/AMP 2015 guidelines.

Met · 2

PM2 SupportingThis variant is present at very low frequency in population databases. gnomAD v2.1 allele frequency is 0.0097% (27/278,536 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency is 0.03% (483/1,614,016 alleles, 0 homozygotes), both below the 0.1% threshold for PM2_supporting. Absent from gnomAD-Canada v1.0. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.0097% (<0.1%)
gnomAD v4.1 AF=0.03% (<0.1%)
gnomAD-Canada: absent
0 homozygotes in all populations.

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.263 (below the typical pathogenic threshold), BayesDel score is −0.147 (negative, consistent with benign), and SpliceAI predicts no splicing impact (max delta 0.01). All three independent in silico predictors converge on a benign or neutral prediction. Details ▾Hide ▴

Evidence considered

REVEL: 0.263
BayesDel: −0.147
SpliceAI max delta: 0.01. Three independent predictors all indicate no significant deleterious effect.

Sources

revelbayesdelspliceai ↗

Not met · 19 · evaluated, threshold not reached

PS1 No known pathogenic missense variant at the same amino acid residue (Thr174) with a different nucleotide change has been established. PS1 requires a previously characterized pathogenic variant at the identical amino acid position. Details ▾Hide ▴

Evidence considered

PM5 candidate harvesting found no same-residue comparator variants
no ClinVar pathogenic/likely pathogenic entries at residue 174.

Sources

pm5_candidates

PS3 No well-established functional studies demonstrate a deleterious effect for p.Thr174Arg. OncoKB classifies this variant as Likely Neutral. REVEL (0.263) and BayesDel (−0.147) support a benign or neutral effect. The comprehensive FGFR functional screen (PMID:34272467) evaluated 160 FGFR variants but did not include Thr174Arg. Details ▾Hide ▴

Evidence considered

OncoKB: Likely Neutral
REVEL score 0.263 (below pathogenic threshold)
BayesDel score −0.147 (benign-leaning)
PMID:34272467 comprehensive FGFR functional screen did not include T174R.

Still missing

No variant-specific functional assay for p.Thr174Arg

Sources

oncokb ↗revelbayesdelPMID:34272467 ↗

PS4 No case-control data demonstrate statistically significant enrichment of this variant in affected individuals compared to controls. Variant is observed at low frequency in gnomAD (27/278,536 in v2.1; 483/1,614,016 in v4.1) but no disease-specific cohort comparison is available. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 27/278
536 (AF=0.0097%)
gnomAD v4.1: 483/1
614
016 (AF=0.03%)
no case-control enrichment analysis available.

Still missing

No case-control studies for this specific variant

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PM1 Residue Thr174 is located in the extracellular Ig-like domain of FGFR1, not in a recognized mutational hotspot. The hotspots analysis confirms this variant does not lie in a statistically significant hotspot. OncoKB classifies as Likely Neutral. No domain-specific enrichment evidence places Thr174 within a critical functional domain without benign variation. Details ▾Hide ▴

Evidence considered

Hotspots analysis: residue not significant
exact variant not listed
OncoKB: Likely Neutral
residue is in extracellular Ig-like domain
not kinase domain.

Sources

oncokb ↗

PM5 No known pathogenic missense variant at the same amino acid residue (Thr174) has been identified. Automated PM5 candidate harvesting found no same-residue comparator variants in ClinVar. Details ▾Hide ▴

Evidence considered

PM5 candidate module: 0 same-residue candidates
no ClinVar P/LP entries at residue 174.

Sources

pm5_candidates

PP1 No segregation data are available for this variant. None of the reviewed publications or ClinVar submissions include co-segregation analysis. Details ▾Hide ▴

Still missing

No family segregation data available

PP2 PP2 requires a low rate of benign missense variation in the gene. FGFR1 has 334 missense variants reported in gnomAD across all domains. While certain domains show regional enrichment for pathogenic variants (Xu 2023, PMID:37805574), the gene as a whole does not meet the threshold of low benign missense variation rate. Details ▾Hide ▴

Evidence considered

Xu 2023 reports domain-specific enrichment but notes population-level benign missense variation exists across FGFR1 domains
gnomAD contains 334 FGFR1 missense variants.

Sources

PMID:37805574 ↗gnomad_v2 ↗

PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.263 (below the typical 0.5 pathogenic threshold), BayesDel score is −0.147 (negative, consistent with benign), and SpliceAI max delta is 0.01 (no predicted splice impact). All in silico predictors suggest a benign or neutral effect. Details ▾Hide ▴

Evidence considered

REVEL: 0.263 (benign-leaning)
BayesDel: −0.147 (benign)
SpliceAI max delta: 0.01 (no splice impact). All tools indicate no significant deleterious effect.

Sources

revelbayesdelspliceai ↗

PP4 No patient-specific phenotype or family history data are available for this variant. PP4 requires that the patient's phenotype or family history be highly specific for a disease with a single genetic etiology. Details ▾Hide ▴

Still missing

No proband phenotype data available for adjudication

PP5 No reputable source classifies this variant as pathogenic. ClinVar consensus is Uncertain significance. OncoKB classifies as Likely Neutral. The GeneReviews cited in ClinVar submissions (PMID:20301509, 20301628, 26937548, 35099867, 38648328) are general gene-level overviews and do not specifically address this variant. Details ▾Hide ▴

Evidence considered

ClinVar: VUS (3 submitters)
OncoKB: Likely Neutral
GeneReviews entries are gene-level and do not mention c.521C>G.

Sources

clinvar ↗oncokb ↗

BA1 Allele frequency is far below the 1% threshold. gnomAD v2.1 AF=0.0097%, gnomAD v4.1 AF=0.03%. This variant is rare in all populations. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.0097%
gnomAD v4.1 AF=0.03%
both far below 1% BA1 threshold.

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 Allele frequency is below the 0.3% threshold. gnomAD v2.1 AF=0.0097%, gnomAD v4.1 AF=0.03%. Highest subpopulation frequency is European (non-Finnish) at 0.019%. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.0097% (<0.3%)
gnomAD v4.1 AF=0.03% (<0.3%)
max subpopulation AF=0.019% (NFE).

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No homozygous individuals are observed in gnomAD. No healthy adult control data with confirmed unaffected status are available for this variant. Without homozygous or confirmed healthy heterozygous carrier data, BS2 cannot be applied. Details ▾Hide ▴

Evidence considered

0 homozygotes in gnomAD v2.1 and v4.1
no confirmed healthy adult carrier data.

Still missing

No homozygous individuals or confirmed healthy adult carriers

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No well-established functional studies demonstrate no deleterious effect for this specific variant. Although OncoKB classifies as Likely Neutral and in silico predictors (REVEL 0.263, BayesDel −0.147) suggest a benign effect, these do not constitute well-established functional studies. The comprehensive FGFR functional screen (PMID:34272467) did not include Thr174Arg. Details ▾Hide ▴

Evidence considered

OncoKB: Likely Neutral
REVEL: 0.263
BayesDel: −0.147
PMID:34272467 did not include T174R in its 160-variant functional panel.

Still missing

No variant-specific functional assay confirming neutral effect

Sources

oncokb ↗revelbayesdelPMID:34272467 ↗

BS4 No segregation or non-segregation data are available for this variant. Details ▾Hide ▴

Still missing

No family segregation data available

BP2 No data are available regarding observation of this variant in trans with a pathogenic variant. No co-occurrence data exist. Details ▾Hide ▴

Still missing

No trans or cis phase data available

BP5 No alternate molecular basis for disease has been identified in a case harboring this variant. No such data are available in the reviewed sources. Details ▾Hide ▴

Still missing

No case data with alternate molecular diagnosis

BP6 No reputable clinical source classifies this variant as benign. ClinVar consensus is Uncertain significance. OncoKB classifies as Likely Neutral, but OncoKB is a somatic cancer knowledgebase and does not constitute a reputable germline clinical classification source. Details ▾Hide ▴

Evidence considered

ClinVar: VUS
OncoKB: Likely Neutral (somatic context).

Sources

clinvar ↗oncokb ↗

PS5 No reputable source classifies this variant as pathogenic. ClinVar consensus is Uncertain significance from all three submitters. OncoKB classifies as Likely Neutral. Details ▾Hide ▴

Evidence considered

ClinVar: VUS (3 submitters
criteria provided
single submitter)
OncoKB: Likely Neutral.

Sources

clinvar ↗oncokb ↗

Not assessed · 2 · no assessment recorded

PS2 No de novo data are available for this variant. None of the reviewed publications or ClinVar submissions include de novo observations. Details ▾Hide ▴

Still missing

No de novo testing or parent-of-origin data available

PM6 No de novo data are available for this variant. None of the reviewed sources include de novo observations. Details ▾Hide ▴

Still missing

No de novo testing data available

Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AMissense substitution (c.521C>G, p.Thr174Arg) does not fall into null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus); generic PVS1 framework is not triggered. Details ▾Hide ▴

Evidence considered

Missense variant in exon 5 of FGFR1 transcript NM_001174067.1
variant bucket classified as 'other' per PVS1 decision algorithm
apply_generic_pvs1_framework is false.

Sources

pvs1_generic_framework ↗pvs1_variant_assessment

PM3 N/AFGFR1-related disorders follow autosomal dominant inheritance. PM3 applies to recessive disorders only. Details ▾Hide ▴

No further detail was recorded.

PM4 N/Ac.521C>G is a single-nucleotide missense substitution, not a protein-length-altering variant (in-frame deletion/insertion or stop-loss). Details ▾Hide ▴

No further detail was recorded.

BP1 N/AFGFR1 disease mechanism includes both missense and truncating pathogenic variants. FGFR1-related Hartsfield syndrome, Kallmann syndrome, and craniosynostosis syndromes are all documented to result from missense variants. BP1 is specific to genes where only truncating variants cause disease. Details ▾Hide ▴

Evidence considered

FGFR1 missense variants are established as pathogenic across multiple syndromes
Xu 2023 (PMID:37805574) documents 95 missense RSVs in IHH probands.

Sources

pvs1_gene_contextPMID:26937548 ↗

BP3 N/AIn-frame deletions/insertions in a repetitive region without known function — not applicable to this missense substitution. Details ▾Hide ▴

No further detail was recorded.

BP7 N/Ac.521C>G is a missense variant (p.Thr174Arg), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

Evidence considered

Missense substitution
BP7 is for synonymous variants only.

Identifiers

Gene: FGFR1
Transcript: NM_001174067.1
Coding (HGVS c.): NM_001174067.1:c.521C>G
Protein (HGVS p.): NP_001167538.1:p.(Thr174Arg)
GRCh38: chr8:38428372 G>C
GRCh37: chr8:38285890 G>C
ClinVar: 1024176
COSMIC: COSV58328267

Gene diagram

Every interpreted variant in FGFR1, mapped onto the exon structure of NM_001174067.1. Select a row to find it on the plot.

FGFR1NM_001174067.1

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 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 483 / 1,614,016 alleles AF 0.000299 · 0 homozygotes · FAF 0.000353

gnomAD v2.1 27 / 278,536 alleles AF 9.69e-05 · 0 homozygotes · FAF 0.00012

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.0003 · 483 / 1,614,016 alleles · 0 hom · FAF 0.00035

Remaining individuals27 / 62,486	0.00043
European (non-Finnish)452 / 1,180,030	0.00038
African/African American3 / 74,924	4e-05
Ashkenazi Jewish1 / 29,608	3.4e-05

0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian.

gnomAD v2.1

AF 9.7e-05 · 27 / 278,536 alleles · 0 hom · FAF 0.00012

European (non-Finnish)24 / 126,298	0.00019
Remaining individuals1 / 7,136	0.00014
African/African American2 / 24,200	8.3e-05

0 alternate alleles recorded in 5 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.000299254; MAF= 0.02993%, 483/1614016 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000432097; MAF= 0.04321%, 27/62486 alleles, homozygotes = 0); grpmax FAF= 0.00035348.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0001085894233901618, 2/18418 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -168 bp

0.000

SpliceAI acceptor gainat -285 bp

0.010

SpliceAI donor lossat -36 bp

0.000

SpliceAI donor gainat -22 bp

0.010

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.020

Other predictors

REVEL: 0.263
BayesDel: -0.147

How the predictions were used

Evidence considered

REVEL: 0.263
BayesDel: −0.147
SpliceAI max delta: 0.01. Three independent predictors all indicate no significant deleterious effect.

Sources

revelbayesdelspliceai ↗

Evidence considered

REVEL: 0.263 (benign-leaning)
BayesDel: −0.147 (benign)
SpliceAI max delta: 0.01 (no splice impact). All tools indicate no significant deleterious effect.

Sources

revelbayesdelspliceai ↗

BP7 N/Ac.521C>G is a missense variant (p.Thr174Arg), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

Evidence considered

Missense substitution
BP7 is for synonymous variants only.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.263. BayesDel score = -0.147005.

8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer.

Comprehensive functional evaluation of 160 FGFR nonsynonymous variants across FGFR1-4 using the MANO method in 3T3 cells. FGFR1 variants evaluated include N546K and K656E as recurrent hotspots. NM_001174067.1:c.521C>G (p.Thr174Arg) was not included in the analyzed variant panel.
Does not name this variant
PMID 34272467 ↗
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. · 2015

ACMG/AMP standards and guidelines for interpretation of sequence variants. This is the foundational framework document; it does not discuss any specific variant.
Does not name this variant
PMID 25741868 ↗
Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency.

Adam MP et al. · 1993

GeneReviews entry on Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. Provides an overview of FGFR1 as a causative gene for IHH/Kallmann syndrome but does not discuss individual variants.
Does not name this variant
PMID 20301509 ↗
FGFR Craniosynostosis Syndromes Overview.

Adam MP et al. · 1993

GeneReviews entry on FGFR Craniosynostosis Syndromes Overview. Discusses FGFR1 in the context of craniosynostosis syndromes generally but does not mention NM_001174067.1:c.521C>G.
Does not name this variant
PMID 20301628 ↗
Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes.

Costa-Barbosa FA et al. · 2013

Phenotypic study of 219 Kallmann syndrome patients prioritizing genetic testing by clinical phenotype. FGFR1/FGF8 pathway variants are associated with dental agenesis and digital bone abnormalities. NM_001174067.1:c.521C>G was not specifically reported.
Does not name this variant
PMID 23533228 ↗
FGFR1-Related Hartsfield Syndrome.

Adam MP et al. · 1993

GeneReviews entry on FGFR1-Related Hartsfield Syndrome. Describes clinical characteristics of Hartsfield syndrome caused by FGFR1 pathogenic variants. Does not discuss the specific variant NM_001174067.1:c.521C>G.
Does not name this variant
PMID 26937548 ↗
Encephalocraniocutaneous Lipomatosis.

Adam MP et al. · 1993

GeneReviews entry on Encephalocraniocutaneous Lipomatosis. FGFR1 is mentioned in the differential diagnosis context but this entry is not FGFR1-specific and does not discuss NM_001174067.1:c.521C>G.
Does not name this variant
PMID 35099867 ↗
How human genetic context can inform pathogenicity classification: FGFR1 variation in idiopathic hypogonadotropic hypogonadism.

Xu W et al. · 2023

Examines FGFR1 missense variant classification in idiopathic hypogonadotropic hypogonadism using domain-based regional enrichment to augment ACMG/AMP criteria. Reports 143 FGFR1 rare sequence variants in 175 IHH probands. NM_001174067.1:c.521C>G (p.Thr174Arg) was not specifically discussed.
Does not name this variant
PMID 37805574 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 483 / 1,614,016 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 2 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

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0001085894233901618, 2/18418 alleles, homozygotes = 0).

ClinVar

Error retrieving ClinVar entry.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.263. BayesDel score = -0.147005.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV58328267, n = 2 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.