rs751753949
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014339.7(IL17RA):āc.1675C>Gā(p.Leu559Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,611,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L559L) has been classified as Likely benign.
Frequency
Consequence
NM_014339.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL17RA | NM_014339.7 | c.1675C>G | p.Leu559Val | missense_variant | 13/13 | ENST00000319363.11 | |
IL17RA | NM_001289905.2 | c.1573C>G | p.Leu525Val | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL17RA | ENST00000319363.11 | c.1675C>G | p.Leu559Val | missense_variant | 13/13 | 1 | NM_014339.7 | P2 | |
IL17RA | ENST00000612619.2 | c.1573C>G | p.Leu525Val | missense_variant | 12/12 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000166 AC: 4AN: 240276Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131188
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1458952Hom.: 0 Cov.: 63 AF XY: 0.00000413 AC XY: 3AN XY: 725684
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74376
ClinVar
Submissions by phenotype
Immunodeficiency 51 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces leucine with valine at codon 559 of the IL17RA protein (p.Leu559Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs751753949, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with IL17RA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at