2-113059446-T-C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_012275.3(IL36RN):c.8T>C(p.Leu3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012275.3 missense
Scores
Clinical Significance
Conservation
Publications
- psoriasis 14, pustularInheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- pustulosis palmaris et plantarisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL36RN | NM_012275.3 | c.8T>C | p.Leu3Pro | missense_variant | Exon 2 of 5 | ENST00000393200.7 | NP_036407.1 | |
IL36RN | NM_173170.1 | c.8T>C | p.Leu3Pro | missense_variant | Exon 2 of 5 | NP_775262.1 | ||
IL36RN | XM_047443918.1 | c.8T>C | p.Leu3Pro | missense_variant | Exon 3 of 6 | XP_047299874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL36RN | ENST00000393200.7 | c.8T>C | p.Leu3Pro | missense_variant | Exon 2 of 5 | 1 | NM_012275.3 | ENSP00000376896.2 | ||
IL36RN | ENST00000346807.7 | c.8T>C | p.Leu3Pro | missense_variant | Exon 2 of 5 | 1 | ENSP00000259212.3 | |||
IL36RN | ENST00000437409.2 | c.8T>C | p.Leu3Pro | missense_variant | Exon 1 of 4 | 1 | ENSP00000409262.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD2 exomes AF: 0.0000239 AC: 6AN: 251466 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727132 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Generalized pustular psoriasis Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3 of the IL36RN protein (p.Leu3Pro). This variant is present in population databases (rs766403906, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with IL36RN-related conditions. 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 disruptive. 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