2-113063237-C-T

Variant names:

• chr2-113063237-C-T
• rs2472188
• NM_012275.3:c.*560C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012275.3(IL36RN):​c.*560C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL36RN NM_012275.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 9 publications found

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]

IL36RN Gene-Disease associations (from GenCC):

• psoriasis 14, pustular

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• pustulosis palmaris et plantaris

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.*560C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.*560C>T		3_prime_UTR_variant	Exon 5 of 5		NP_775262.1
IL36RN	XM_047443918.1	c.*560C>T		3_prime_UTR_variant	Exon 6 of 6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.*560C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.*560C>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000259212.3
IL36RN	ENST00000514072.1	c.*49+511C>T		intron_variant	Intron 1 of 1	3		ENSP00000475308.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 19038 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9832

African (AFR) AF: 0.00 AC: 0 AN: 490

American (AMR) AF: 0.00 AC: 0 AN: 3178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 282

East Asian (EAS) AF: 0.00 AC: 0 AN: 1398

South Asian (SAS) AF: 0.00 AC: 0 AN: 2406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9990

Other (OTH) AF: 0.00 AC: 0 AN: 896

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.88
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2472188; hg19: chr2-113820814;