2-113059094-G-C

Variant names:

• chr2-113059094-G-C
• rs759570472
• ENST00000346807.7:c.-27-318G>C

Variant summary

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

The ENST00000346807.7(IL36RN):​c.-27-318G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 233,478 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: 0.0000043 (0 hom.)
• Consequence: IL36RN ENST00000346807.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 0 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=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_173170.1	c.-27-318G>C		intron_variant	Intron 1 of 4		NP_775262.1
IL36RN	XM_047443918.1	c.-136-39G>C		intron_variant	Intron 1 of 5		XP_047299874.1
IL36RN	NM_012275.3	c.-175G>C		upstream_gene_variant		ENST00000393200.7	NP_036407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000346807.7	c.-27-318G>C		intron_variant	Intron 1 of 4	1		ENSP00000259212.3
IL36RN	ENST00000393200.7	c.-175G>C		upstream_gene_variant		1	NM_012275.3	ENSP00000376896.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000428 AC: 1 AN: 233478 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122454

African (AFR) AF: 0.00 AC: 0 AN: 7644

American (AMR) AF: 0.00 AC: 0 AN: 11978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6888

East Asian (EAS) AF: 0.00 AC: 0 AN: 13938

South Asian (SAS) AF: 0.0000331 AC: 1 AN: 30176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 137134

Other (OTH) AF: 0.00 AC: 0 AN: 13366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		0.41
PromoterAI		0.068	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs759570472; hg19: chr2-113816671;