ENST00000470826.5:n.1454C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000470826.5(FGFR1):n.1454C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 397,934 control chromosomes in the GnomAD database, including 8,798 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3211 hom., cov: 32)

Exomes 𝑓: 0.20 ( 5587 hom. )

Consequence

FGFR1
ENST00000470826.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.629

Publications

26 publications found

Variant links:

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:

ENSG00000255201 (HGNC:):

ENSG00000255201 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFR1	NM_023110.3 link	c.936+369C>T		intron_variant	Intron 7 of 17	ENST00000447712.7	NP_075598.2	P11362-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGFR1	ENST00000447712.7 link	c.936+369C>T	intron_variant	Intron 7 of 17	1	NM_023110.3	ENSP00000400162.2	P11362-1
FGFR1	ENST00000397091.9 link	c.930+369C>T	intron_variant	Intron 7 of 17	1		ENSP00000380280.5	P11362-7
FGFR1	ENST00000397108.8 link	c.930+369C>T	intron_variant	Intron 8 of 18	1		ENSP00000380297.4	P11362-7
FGFR1	ENST00000397113.6 link	c.930+369C>T	intron_variant	Intron 7 of 17	2		ENSP00000380302.2	P11362-7
FGFR1	ENST00000356207.9 link	c.669+369C>T	intron_variant	Intron 6 of 16	1		ENSP00000348537.5	P11362-3
FGFR1	ENST00000397103.5 link	c.663+369C>T	intron_variant	Intron 5 of 15	5		ENSP00000380292.1	E7EU09
FGFR1	ENST00000326324.10 link	c.663+369C>T	intron_variant	Intron 6 of 16	1		ENSP00000327229.6	P11362-14
FGFR1	ENST00000487647.5 link	n.*627+369C>T	intron_variant	Intron 6 of 11	1		ENSP00000435254.1	E9PKX3

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28952

AN:

151966

Hom.:

3204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.314

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.204

AC:

50274

AN:

245850

Hom.:

5587

Cov.:

AF XY:

0.196

AC XY:

25871

AN XY:

132072

show subpopulations

African (AFR)

AF:

0.0983

AC:

708

AN:

7204

American (AMR)

AF:

0.222

AC:

2676

AN:

12072

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

1010

AN:

6536

East Asian (EAS)

AF:

0.323

AC:

4085

AN:

12638

South Asian (SAS)

AF:

0.113

AC:

4575

AN:

40452

European-Finnish (FIN)

AF:

0.182

AC:

2647

AN:

14566

Middle Eastern (MID)

AF:

0.203

AC:

474

AN:

2330

European-Non Finnish (NFE)

AF:

0.229

AC:

31422

AN:

137112

Other (OTH)

AF:

0.207

AC:

2677

AN:

12940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1884

3768

5652

7536

9420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<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:

0.191

AC:

28976

AN:

152084

Hom.:

3211

Cov.:

AF XY:

0.187

AC XY:

13871

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.102

AC:

4221

AN:

41490

American (AMR)

AF:

0.224

AC:

3428

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

536

AN:

3470

East Asian (EAS)

AF:

0.315

AC:

1625

AN:

5162

South Asian (SAS)

AF:

0.103

AC:

498

AN:

4822

European-Finnish (FIN)

AF:

0.186

AC:

1965

AN:

10570

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15876

AN:

67980

Other (OTH)

AF:

0.201

AC:

422

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1146

2292

3438

4584

5730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.218

Hom.:

10463

Bravo

AF:

0.197

Asia WGS

AF:

0.197

AC:

683

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

8.0

(source)

DANN

Benign

0.71

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over