NM_012275.3:c.29+290C>T

Variant names:

• chr2-113059757-C-T
• rs7575934
• NM_012275.3:c.29+290C>T

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+290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,226 control chromosomes in the GnomAD database, including 1,104 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 0.074 (1104 hom., cov: 32)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.29+290C>T		intron_variant	Intron 2 of 4	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.29+290C>T		intron_variant	Intron 2 of 4		NP_775262.1
IL36RN	XM_047443918.1	c.29+290C>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+290C>T		intron_variant	Intron 2 of 4	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.29+290C>T		intron_variant	Intron 2 of 4	1		ENSP00000259212.3
IL36RN	ENST00000437409.2	c.29+290C>T		intron_variant	Intron 1 of 3	1		ENSP00000409262.2

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11261 AN: 152108 Hom.: 1102 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.0585

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

GnomAD4 genome AF: 0.0741 AC: 11283 AN: 152226 Hom.: 1104 Cov.: 32 AF XY: 0.0742 AC XY: 5524 AN XY: 74422

African (AFR) AF: 0.215 AC: 8914 AN: 41506

American (AMR) AF: 0.0298 AC: 455 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1146 AN: 5178

South Asian (SAS) AF: 0.101 AC: 487 AN: 4828

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00148 AC: 101 AN: 68016

Other (OTH) AF: 0.0583 AC: 123 AN: 2108

Alfa AF: 0.0250 Hom.: 385

Bravo AF: 0.0833

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		0.025
PromoterAI		0.0091	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: rs7575934; hg19: chr2-113817334;