rs869025669
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_023110.3(FGFR1):c.572T>C(p.Leu191Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
FGFR1
NM_023110.3 missense
NM_023110.3 missense
Scores
8
10
1
Clinical Significance
Conservation
PhyloP100: 4.21
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a domain Ig-like C2-type 2 (size 88) in uniprot entity FGFR1_HUMAN there are 29 pathogenic changes around while only 1 benign (97%) in NM_023110.3
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the FGFR1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 93 curated pathogenic missense variants (we use a threshold of 10). The gene has 28 curated benign missense variants. Gene score misZ: 2.4852 (below the threshold of 3.09). Trascript score misZ: 4.2642 (above the threshold of 3.09). GenCC associations: The gene is linked to hypogonadotropic hypogonadism 2 with or without anosmia, encephalocraniocutaneous lipomatosis, hypogonadotropic hypogonadism, tooth agenesis, isolated trigonocephaly, Pfeiffer syndrome type 1, Jackson-Weiss syndrome, Pfeiffer syndrome, Kallmann syndrome, septooptic dysplasia, hypogonadotropic hypogonadism 7 with or without anosmia, holoprosencephaly, osteoglophonic dwarfism, Hartsfield-Bixler-Demyer syndrome.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.842
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FGFR1 | ENST00000447712.7 | c.572T>C | p.Leu191Ser | missense_variant | Exon 5 of 18 | 1 | NM_023110.3 | ENSP00000400162.2 | ||
| FGFR1 | ENST00000397091.9 | c.566T>C | p.Leu189Ser | missense_variant | Exon 5 of 18 | 1 | ENSP00000380280.5 | |||
| FGFR1 | ENST00000397108.8 | c.566T>C | p.Leu189Ser | missense_variant | Exon 6 of 19 | 1 | ENSP00000380297.4 | |||
| FGFR1 | ENST00000397113.6 | c.566T>C | p.Leu189Ser | missense_variant | Exon 5 of 18 | 2 | ENSP00000380302.2 | |||
| FGFR1 | ENST00000356207.9 | c.305T>C | p.Leu102Ser | missense_variant | Exon 4 of 17 | 1 | ENSP00000348537.5 | |||
| FGFR1 | ENST00000397103.5 | c.299T>C | p.Leu100Ser | missense_variant | Exon 3 of 16 | 5 | ENSP00000380292.1 | |||
| FGFR1 | ENST00000326324.10 | c.299T>C | p.Leu100Ser | missense_variant | Exon 4 of 17 | 1 | ENSP00000327229.6 | |||
| FGFR1 | ENST00000487647.5 | n.*263T>C | non_coding_transcript_exon_variant | Exon 4 of 12 | 1 | ENSP00000435254.1 | ||||
| FGFR1 | ENST00000487647.5 | n.*263T>C | 3_prime_UTR_variant | Exon 4 of 12 | 1 | ENSP00000435254.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Hartsfield-Bixler-Demyer syndrome Other:1
-
GeneReviews
Significance: not provided
Review Status: no classification provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D;T;.;.;.;.;.;.;T;.;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M;.;.;M;.;.;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;.;.;.;D
Polyphen
D;D;D;D;.;D;D;D;D;D;.;D;.;.;.;.
Vest4
MutPred
0.59
.;.;Gain of disorder (P = 0.0054);.;.;Gain of disorder (P = 0.0054);.;.;.;.;.;.;.;Gain of disorder (P = 0.0054);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at