2-113059989-T-C

Variant names:

• chr2-113059989-T-C
• rs1530551
• NM_012275.3:c.29+522T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012275.3(IL36RN):​c.29+522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,082 control chromosomes in the GnomAD database, including 36,753 homozygotes. 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: 𝑓 0.69 (36753 hom., cov: 32)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36RN	NM_012275.3	MANE Select	c.29+522T>C		intron	N/A	NP_036407.1
	IL36RN	NM_173170.1		c.29+522T>C		intron	N/A	NP_775262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL36RN	ENST00000393200.7	TSL:1 MANE Select	c.29+522T>C		intron	N/A	ENSP00000376896.2
	IL36RN	ENST00000346807.7	TSL:1	c.29+522T>C		intron	N/A	ENSP00000259212.3
	IL36RN	ENST00000437409.2	TSL:1	c.29+522T>C		intron	N/A	ENSP00000409262.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104488 AN: 151964 Hom.: 36700 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.688 AC: 104593 AN: 152082 Hom.: 36753 Cov.: 32 AF XY: 0.693 AC XY: 51503 AN XY: 74334

African (AFR) AF: 0.788 AC: 32699 AN: 41502

American (AMR) AF: 0.677 AC: 10347 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2432 AN: 3470

East Asian (EAS) AF: 0.931 AC: 4810 AN: 5168

South Asian (SAS) AF: 0.901 AC: 4342 AN: 4820

European-Finnish (FIN) AF: 0.631 AC: 6668 AN: 10566

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40884 AN: 67946

Other (OTH) AF: 0.711 AC: 1502 AN: 2112

Alfa AF: 0.638 Hom.: 111346

Bravo AF: 0.696

Asia WGS AF: 0.913 AC: 3172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs1530551; hg19: chr2-113817566;