rs4647942
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001004356.3(FGFRL1):c.60G>A(p.Pro20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,485,428 control chromosomes in the GnomAD database, including 169,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.53 ( 22012 hom., cov: 35)
Exomes 𝑓: 0.47 ( 147372 hom. )
Consequence
FGFRL1
NM_001004356.3 synonymous
NM_001004356.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.76
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=-0.54).
BP6
?
Variant 4-1012545-G-A is Benign according to our data. Variant chr4-1012545-G-A is described in ClinVar as [Benign]. Clinvar id is 1169548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFRL1 | NM_001004356.3 | c.60G>A | p.Pro20= | synonymous_variant | 2/7 | ENST00000510644.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFRL1 | ENST00000510644.6 | c.60G>A | p.Pro20= | synonymous_variant | 2/7 | 1 | NM_001004356.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.526 AC: 79868AN: 151962Hom.: 21979 Cov.: 35
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GnomAD3 exomes AF: 0.461 AC: 49662AN: 107680Hom.: 11588 AF XY: 0.452 AC XY: 27479AN XY: 60840
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GnomAD4 exome AF: 0.468 AC: 623409AN: 1333354Hom.: 147372 Cov.: 24 AF XY: 0.464 AC XY: 306066AN XY: 660330
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GnomAD4 genome ? AF: 0.526 AC: 79965AN: 152074Hom.: 22012 Cov.: 35 AF XY: 0.518 AC XY: 38470AN XY: 74330
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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 | Oct 21, 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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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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