chr2-113062578-G-T

Position:

• chr2-113062578-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012275.3(IL36RN):​c.369G>T​(p.Thr123Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T123T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL36RN NM_012275.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP7: Synonymous conserved (PhyloP=-4.89 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.369G>T	p.Thr123Thr	synonymous_variant	5/5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.369G>T	p.Thr123Thr	synonymous_variant	5/5		NP_775262.1
IL36RN	XM_047443918.1	c.369G>T	p.Thr123Thr	synonymous_variant	6/6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.369G>T	p.Thr123Thr	synonymous_variant	5/5	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.369G>T	p.Thr123Thr	synonymous_variant	5/5	1		ENSP00000259212.3
IL36RN	ENST00000437409.2	c.369G>T	p.Thr123Thr	synonymous_variant	4/4	1		ENSP00000409262.2
IL36RN	ENST00000514072.1	c.57G>T	p.Thr19Thr	synonymous_variant	1/2	3		ENSP00000475308.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs28938778; hg19: chr2-113820155;