ClinVar Miner

Submissions for variant NM_173170.1(IL36RN):c.115+6T>C (rs148755083)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000033132 SCV000949734 pathogenic Pustular psoriasis, generalized 2018-11-21 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the IL36RN gene. It does not directly change the encoded amino acid sequence of the IL36RN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs148755083, ExAC 1.4%). This variant has been observed in numerous individuals and families affected with generalized pustular psoriasis and has been reported as a possible founder mutation in Japanese and Chinese populations (PMID: 22903787, 24979538, 23863864, 23698098, 23303454, 26589685, 28063630). ClinVar contains an entry for this variant (Variation ID: 40005). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this intronic change causes skipping of exon 3, resulting in a truncated protein product (PMID: 23698098, 22903787). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000033132 SCV001135931 benign Pustular psoriasis, generalized 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000033132 SCV001288877 uncertain significance Pustular psoriasis, generalized 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000033132 SCV000056913 pathogenic Pustular psoriasis, generalized 2013-11-01 no assertion criteria provided literature only
Reproductive Health Research and Development,BGI Genomics RCV000033132 SCV001142321 pathogenic Pustular psoriasis, generalized 2020-01-06 no assertion criteria provided curation NG_031864.1(NM_012275.2):c.115+6T>C in the IL36RN gene has an allele frequency of 0.013 in East Asian subpopulation in the gnomAD database. Farooq M et al. reported one patient with generalized pustular psoriasis was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg) and another was compound heterozygous for mutations c.28C>T (p.Arg10*) and c.115+6T>C in the IL36RN gene (PMID: 22903787). Shu D et al. reported two siblings with deficiency of IL-36Ra, from a Chinese Daur family, who both carried the homozygous IL36RN c.115+6T>C mutation, while other four healthy family members carried heterozygous c.115+6T>C mutations (PMID: 24979538). Experimental studies have shown that this intronic change causes skipping of exon 3, resulting in a truncated protein product (PMID: 23698098; 22903787). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PS3, PM3_Strong, PP1, PP4.

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