5-76832887-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005242.6(F2RL1):c.280G>A(p.Gly94Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000384 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
F2RL1
NM_005242.6 missense
NM_005242.6 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 4.70
Genes affected
F2RL1 (HGNC:3538): (F2R like trypsin receptor 1) This gene encodes a member of the G-protein coupled receptor 1 family of proteins. The encoded cell surface receptor is activated through proteolytic cleavage of its extracellular amino terminus, resulting in a new amino terminus that acts as a tethered ligand that binds to an extracellular loop domain. Activation of the receptor has been shown to stimulate vascular smooth muscle relaxation, dilate blood vessels, increase blood flow, and lower blood pressure. This protein is also important in the inflammatory response, as well as innate and adaptive immunity. [provided by RefSeq, Jun 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16325054).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F2RL1 | NM_005242.6 | c.280G>A | p.Gly94Ser | missense_variant | 2/2 | ENST00000296677.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F2RL1 | ENST00000296677.5 | c.280G>A | p.Gly94Ser | missense_variant | 2/2 | 1 | NM_005242.6 | P1 | |
F2RL1 | ENST00000514165.1 | c.-3G>A | 5_prime_UTR_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152160Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251452Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461892Hom.: 0 Cov.: 70 AF XY: 0.0000344 AC XY: 25AN XY: 727248
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2022 | The c.280G>A (p.G94S) alteration is located in exon 2 (coding exon 2) of the F2RL1 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the glycine (G) at amino acid position 94 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
D
GERP RS
gMVP
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