rs17175898

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_023110.3(FGFR1):c.600C>T(p.Asp200Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,246 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 117 hom. )

Consequence

FGFR1
NM_023110.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.180

Publications

5 publications found

Variant links:

COSMIC-nc: COSV58336953

Genes affected

FGFR1 (HGNC:3688): (fibroblast growth factor receptor 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

FGFR1 Gene-Disease associations (from GenCC):

encephalocraniocutaneous lipomatosis
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Hartsfield-Bixler-Demyer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen
hypogonadotropic hypogonadism 2 with or without anosmia
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
osteoglophonic dysplasia
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Pfeiffer syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
Pfeiffer syndrome type 1
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Jackson-Weiss syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated trigonocephaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FGFR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-38427942-G-A is Benign according to our data. Variant chr8-38427942-G-A is described in ClinVar as Benign. ClinVar VariationId is 362901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.18 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00757 (1154/152356) while in subpopulation AMR AF = 0.0145 (222/15308). AF 95% confidence interval is 0.0129. There are 7 homozygotes in GnomAd4. There are 547 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1	NM_023110.3 link	c.600C>T	p.Asp200Asp	synonymous_variant	Exon 5 of 18	ENST00000447712.7	NP_075598.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FGFR1	ENST00000447712.7 link	c.600C>T	p.Asp200Asp	synonymous_variant	Exon 5 of 18	1	NM_023110.3	ENSP00000400162.2
FGFR1	ENST00000397091.9 link	c.594C>T	p.Asp198Asp	synonymous_variant	Exon 5 of 18	1		ENSP00000380280.5
FGFR1	ENST00000397108.8 link	c.594C>T	p.Asp198Asp	synonymous_variant	Exon 6 of 19	1		ENSP00000380297.4
FGFR1	ENST00000397113.6 link	c.594C>T	p.Asp198Asp	synonymous_variant	Exon 5 of 18	2		ENSP00000380302.2
FGFR1	ENST00000356207.9 link	c.333C>T	p.Asp111Asp	synonymous_variant	Exon 4 of 17	1		ENSP00000348537.5
FGFR1	ENST00000397103.5 link	c.327C>T	p.Asp109Asp	synonymous_variant	Exon 3 of 16	5		ENSP00000380292.1
FGFR1	ENST00000326324.10 link	c.327C>T	p.Asp109Asp	synonymous_variant	Exon 4 of 17	1		ENSP00000327229.6
FGFR1	ENST00000487647.5 link	n.*291C>T		non_coding_transcript_exon_variant	Exon 4 of 12	1		ENSP00000435254.1
FGFR1	ENST00000487647.5 link	n.*291C>T		3_prime_UTR_variant	Exon 4 of 12	1		ENSP00000435254.1

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1153

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00812

AC:

2027

AN:

249560

AF XY:

0.00799

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00964

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00686

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00940

GnomAD4 exome

AF:

0.0108

AC:

15746

AN:

1461890

Hom.:

117

Cov.:

AF XY:

0.0105

AC XY:

7609

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00970

AC:

434

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00976

AC:

255

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00194

AC:

167

AN:

86258

European-Finnish (FIN)

AF:

0.00694

AC:

371

AN:

53420

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0125

AC:

13863

AN:

1112008

Other (OTH)

AF:

0.00974

AC:

588

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

921

1842

2764

3685

4606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00757

AC:

1154

AN:

152356

Hom.:

Cov.:

AF XY:

0.00734

AC XY:

547

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41574

American (AMR)

AF:

0.0145

AC:

222

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00537

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

730

AN:

68038

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00921

Hom.:

Bravo

AF:

0.00808

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Feb 09, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30733481, 16764984, 20696889, 17963255) -

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FGFR1: BP4, BS1 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Trigonocephaly 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypogonadotropic hypogonadism 2 with or without anosmia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pfeiffer syndrome;C0406612:Encephalocraniocutaneous lipomatosis;C0432122:Trigonocephaly 1;C0432283:Osteoglophonic dysplasia;C0795998:Jackson-Weiss syndrome;C1563720:Hypogonadotropic hypogonadism 2 with or without anosmia;C1845146:Hartsfield-Bixler-Demyer syndrome

Benign:1

Apr 03, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Osteoglophonic dysplasia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pfeiffer syndrome;C1563720:Hypogonadotropic hypogonadism 2 with or without anosmia

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Craniosynostosis syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.18

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over