rs766403906

Variant names:

• chr2-113059446-T-A
• rs766403906
• NM_012275.3:c.8T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113059446-T-A
• chr2-113059446-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012275.3(IL36RN):​c.8T>A​(p.Leu3Gln) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL36RN NM_012275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40496528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.8T>A	p.Leu3Gln	missense_variant	Exon 2 of 5	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.8T>A	p.Leu3Gln	missense_variant	Exon 2 of 5		NP_775262.1
IL36RN	XM_047443918.1	c.8T>A	p.Leu3Gln	missense_variant	Exon 3 of 6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.8T>A	p.Leu3Gln	missense_variant	Exon 2 of 5	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.8T>A	p.Leu3Gln	missense_variant	Exon 2 of 5	1		ENSP00000259212.3
IL36RN	ENST00000437409.2	c.8T>A	p.Leu3Gln	missense_variant	Exon 1 of 4	1		ENSP00000409262.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.6	L;L;.
PhyloP100		2.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.34	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.53
MutPred		0.40		Gain of disorder (P = 0.0117);Gain of disorder (P = 0.0117);Gain of disorder (P = 0.0117);
MVP		0.86
MPC		0.53
ClinPred		0.93	D
GERP RS		4.4
PromoterAI		0.013	Neutral
Varity_R		0.19
gMVP		0.51
Mutation Taster		=73/27	polymorphism

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: rs766403906; hg19: chr2-113817023;