2-113062578-G-C

Position:

chr2-113062578-G-C

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 529888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113062578-G-C is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL36RN	NM_012275.3 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	5/5	ENST00000393200.7	NP_036407.1	Q9UBH0A0A024R518
IL36RN	NM_173170.1 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	5/5		NP_775262.1	Q9UBH0A0A024R518
IL36RN	XM_047443918.1 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	6/6		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL36RN	ENST00000393200.7 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	5/5	1	NM_012275.3	ENSP00000376896.2	Q9UBH0
IL36RN	ENST00000346807.7 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	5/5	1		ENSP00000259212.3	Q9UBH0
IL36RN	ENST00000437409.2 linkuse as main transcript	c.369G>C	p.Thr123Thr	synonymous_variant	4/4	1		ENSP00000409262.2	Q9UBH0C9JTH1
IL36RN	ENST00000514072.1 linkuse as main transcript	c.57G>C	p.Thr19Thr	synonymous_variant	1/2	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

GnomAD3 exomes

AF:

0.00167

AC:

420

AN:

251108

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135774

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 SAS 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

Gnomad4 AFR exome

AF:

0.0235

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00657

AC:

1000

AN:

152214

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autoinflammatory syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 01, 2019

- -

Generalized pustular psoriasis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0090

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over