rs151274071
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The ENST00000393200.7(IL36RN):c.363G>A(p.Leu121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,613,942 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00084 ( 0 hom. )
Consequence
IL36RN
ENST00000393200.7 synonymous
ENST00000393200.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.74
Genes affected
IL36RN (HGNC:15561): (interleukin 36 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine was shown to specifically inhibit the activation of NF-kappaB induced by interleukin 1 family, member 6 (IL1F6). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 2-113062572-G-A is Benign according to our data. Variant chr2-113062572-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 330780.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BP7
Synonymous conserved (PhyloP=-1.74 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL36RN | NM_012275.3 | c.363G>A | p.Leu121= | synonymous_variant | 5/5 | ENST00000393200.7 | NP_036407.1 | |
IL36RN | NM_173170.1 | c.363G>A | p.Leu121= | synonymous_variant | 5/5 | NP_775262.1 | ||
IL36RN | XM_047443918.1 | c.363G>A | p.Leu121= | synonymous_variant | 6/6 | XP_047299874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL36RN | ENST00000393200.7 | c.363G>A | p.Leu121= | synonymous_variant | 5/5 | 1 | NM_012275.3 | ENSP00000376896 | P1 | |
IL36RN | ENST00000346807.7 | c.363G>A | p.Leu121= | synonymous_variant | 5/5 | 1 | ENSP00000259212 | P1 | ||
IL36RN | ENST00000437409.2 | c.363G>A | p.Leu121= | synonymous_variant | 4/4 | 1 | ENSP00000409262 | P1 | ||
IL36RN | ENST00000514072.1 | c.54G>A | p.Leu18= | synonymous_variant | 1/2 | 3 | ENSP00000475308 |
Frequencies
GnomAD3 genomes AF: 0.000677 AC: 103AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000522 AC: 131AN: 251150Hom.: 0 AF XY: 0.000508 AC XY: 69AN XY: 135796
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GnomAD4 exome AF: 0.000841 AC: 1229AN: 1461672Hom.: 0 Cov.: 32 AF XY: 0.000820 AC XY: 596AN XY: 727154
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GnomAD4 genome AF: 0.000676 AC: 103AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74442
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Generalized pustular psoriasis Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 22, 2023 | - - |
Autoinflammatory syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 14, 2022 | - - |
IL36RN-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 14, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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