rs753549556
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The ENST00000319363.11(IL17RA):c.1951G>A(p.Glu651Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000575 in 1,529,510 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E651A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000319363.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL17RA | NM_014339.7 | c.1951G>A | p.Glu651Lys | missense_variant | 13/13 | ENST00000319363.11 | NP_055154.3 | |
IL17RA | NM_001289905.2 | c.1849G>A | p.Glu617Lys | missense_variant | 12/12 | NP_001276834.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL17RA | ENST00000319363.11 | c.1951G>A | p.Glu651Lys | missense_variant | 13/13 | 1 | NM_014339.7 | ENSP00000320936 | P2 | |
IL17RA | ENST00000612619.2 | c.1849G>A | p.Glu617Lys | missense_variant | 12/12 | 5 | ENSP00000479970 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152198Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000147 AC: 19AN: 129376Hom.: 0 AF XY: 0.0000850 AC XY: 6AN XY: 70550
GnomAD4 exome AF: 0.0000378 AC: 52AN: 1377194Hom.: 0 Cov.: 43 AF XY: 0.0000309 AC XY: 21AN XY: 679138
GnomAD4 genome AF: 0.000236 AC: 36AN: 152316Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16AN XY: 74484
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2022 | The c.1951G>A (p.E651K) alteration is located in exon 13 (coding exon 13) of the IL17RA gene. This alteration results from a G to A substitution at nucleotide position 1951, causing the glutamic acid (E) at amino acid position 651 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Immunodeficiency 51 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 651 of the IL17RA protein (p.Glu651Lys). This variant is present in population databases (rs753549556, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with IL17RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 542918). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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