chr2-113062578-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012275.3(IL36RN):c.369G>C(p.Thr123Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,826 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T123T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0066 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 6 hom. )

Consequence

IL36RN
NM_012275.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.89

Publications

2 publications found

Variant links:

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

IL36RN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP6

Variant 2-113062578-G-C is Benign according to our data. Variant chr2-113062578-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 529888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00657 (1000/152214) while in subpopulation AFR AF = 0.023 (957/41530). AF 95% confidence interval is 0.0218. There are 14 homozygotes in GnomAd4. There are 481 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 5 of 5	ENST00000393200.7	NP_036407.1	Q9UBH0A0A024R518
IL36RN	NM_173170.1 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 5 of 5		NP_775262.1	Q9UBH0A0A024R518
IL36RN	XM_047443918.1 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 6 of 6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL36RN	ENST00000393200.7 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 5 of 5	1	NM_012275.3	ENSP00000376896.2	Q9UBH0
IL36RN	ENST00000346807.7 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 5 of 5	1		ENSP00000259212.3	Q9UBH0
IL36RN	ENST00000437409.2 link	c.369G>C	p.Thr123Thr	synonymous_variant	Exon 4 of 4	1		ENSP00000409262.2	Q9UBH0C9JTH1
IL36RN	ENST00000514072.1 link	c.57G>C	p.Thr19Thr	synonymous_variant	Exon 1 of 2	3		ENSP00000475308.1	U3KPW9

Frequencies

GnomAD3 genomes

AF:

0.00659

AC:

1002

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00167

AC:

420

AN:

251108

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000644

AC:

942

AN:

1461612

Hom.:

Cov.:

AF XY:

0.000573

AC XY:

417

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.0235

AC:

787

AN:

33478

American (AMR)

AF:

0.000760

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1112012

Other (OTH)

AF:

0.00147

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00657

AC:

1000

AN:

152214

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0230

AC:

957

AN:

41530

American (AMR)

AF:

0.00222

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68000

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000652

Hom.:

Bravo

AF:

0.00778

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autoinflammatory syndrome

Benign:1

Nov 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Generalized pustular psoriasis

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0090

(source)

DANN

Benign

0.58

PhyloP100

-4.9

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over