rs4647933
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001004356.3(FGFRL1):c.433+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,558,602 control chromosomes in the GnomAD database, including 1,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.034 ( 134 hom., cov: 31)
Exomes 𝑓: 0.041 ( 1406 hom. )
Consequence
FGFRL1
NM_001004356.3 intron
NM_001004356.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.406
Genes affected
FGFRL1 (HGNC:3693): (fibroblast growth factor receptor like 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 would consist 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. A marked difference between this gene product and the other family members is its lack of a cytoplasmic tyrosine kinase domain. The result is a transmembrane receptor that could interact with other family members and potentially inhibit signaling. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 4-1023731-G-C is Benign according to our data. Variant chr4-1023731-G-C is described in ClinVar as [Benign]. Clinvar id is 1170809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFRL1 | NM_001004356.3 | c.433+10G>C | intron_variant | ENST00000510644.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFRL1 | ENST00000510644.6 | c.433+10G>C | intron_variant | 1 | NM_001004356.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0342 AC: 5197AN: 152034Hom.: 132 Cov.: 31
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GnomAD3 exomes AF: 0.0478 AC: 7735AN: 161912Hom.: 258 AF XY: 0.0466 AC XY: 4090AN XY: 87804
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GnomAD4 exome AF: 0.0407 AC: 57263AN: 1406452Hom.: 1406 Cov.: 46 AF XY: 0.0402 AC XY: 27914AN XY: 694356
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GnomAD4 genome ? AF: 0.0343 AC: 5212AN: 152150Hom.: 134 Cov.: 31 AF XY: 0.0344 AC XY: 2556AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
FGFRL1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 23, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at