2-113059604-C-T

Variant names:

• chr2-113059604-C-T
• rs2515392
• NM_012275.3:c.29+137C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012275.3(IL36RN):​c.29+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 949,194 control chromosomes in the GnomAD database, including 215,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36722 hom., cov: 30)
  • Exomes 𝑓: 0.66 (179070 hom.)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.393
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-113059604-C-T is Benign according to our data. Variant chr2-113059604-C-T is described in ClinVar as [Benign]. Clinvar id is 2628183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.29+137C>T		intron_variant	Intron 2 of 4	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.29+137C>T		intron_variant	Intron 2 of 4		NP_775262.1
IL36RN	XM_047443918.1	c.29+137C>T		intron_variant	Intron 3 of 5		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.29+137C>T		intron_variant	Intron 2 of 4	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.29+137C>T		intron_variant	Intron 2 of 4	1		ENSP00000259212.3
IL36RN	ENST00000437409.2	c.29+137C>T		intron_variant	Intron 1 of 3	1		ENSP00000409262.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104405 AN: 151844 Hom.: 36669 Cov.: 30

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.660 AC: 526178 AN: 797232 Hom.: 179070 AF XY: 0.669 AC XY: 278938 AN XY: 417136

African (AFR) AF: 0.792 AC: 16322 AN: 20610

American (AMR) AF: 0.706 AC: 25331 AN: 35904

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 14297 AN: 20732

East Asian (EAS) AF: 0.945 AC: 33344 AN: 35274

South Asian (SAS) AF: 0.888 AC: 60771 AN: 68398

European-Finnish (FIN) AF: 0.622 AC: 31195 AN: 50146

Middle Eastern (MID) AF: 0.757 AC: 2148 AN: 2836

European-Non Finnish (NFE) AF: 0.604 AC: 317057 AN: 525356

Other (OTH) AF: 0.677 AC: 25713 AN: 37976

GnomAD4 genome AF: 0.688 AC: 104510 AN: 151962 Hom.: 36722 Cov.: 30 AF XY: 0.693 AC XY: 51434 AN XY: 74260

African (AFR) AF: 0.788 AC: 32694 AN: 41474

American (AMR) AF: 0.676 AC: 10342 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2428 AN: 3466

East Asian (EAS) AF: 0.931 AC: 4791 AN: 5146

South Asian (SAS) AF: 0.901 AC: 4343 AN: 4822

European-Finnish (FIN) AF: 0.630 AC: 6645 AN: 10540

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40860 AN: 67914

Other (OTH) AF: 0.711 AC: 1499 AN: 2108

Alfa AF: 0.626 Hom.: 3746

Bravo AF: 0.696

Asia WGS AF: 0.913 AC: 3173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.66
PhyloP100		-0.39
PromoterAI		-0.0034	Neutral
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: rs2515392; hg19: chr2-113817181;