chr2-113062899-T-A

Variant names:

• chr2-113062899-T-A
• rs2515401
• NM_012275.3:c.*222T>A

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.*222T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 437,752 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: IL36RN NM_012275.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 13 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=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.*222T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.*222T>A		3_prime_UTR_variant	Exon 5 of 5		NP_775262.1
IL36RN	XM_047443918.1	c.*222T>A		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.*222T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.*222T>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000259212.3
IL36RN	ENST00000514072.1	c.*49+173T>A		intron_variant	Intron 1 of 1	3		ENSP00000475308.1
IL36RN	ENST00000437409.2	c.*222T>A		downstream_gene_variant		1		ENSP00000409262.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000114 AC: 5 AN: 437752 Hom.: 0 Cov.: 3 AF XY: 0.0000173 AC XY: 4 AN XY: 231792

African (AFR) AF: 0.00 AC: 0 AN: 12486

American (AMR) AF: 0.00 AC: 0 AN: 21022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13584

East Asian (EAS) AF: 0.000103 AC: 3 AN: 29184

South Asian (SAS) AF: 0.0000212 AC: 1 AN: 47066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1914

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 260572

Other (OTH) AF: 0.0000399 AC: 1 AN: 25074

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 37045

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.26
DANN	Benign	0.55
PhyloP100		-2.8
PromoterAI		-0.021	Neutral

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: rs2515401; hg19: chr2-113820476;