Variant 2-113059363-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012275.3(IL36RN):c.-27-49C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,538,496 control chromosomes in the GnomAD database, including 130,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 9730 hom., cov: 32)

Exomes 𝑓: 0.41 ( 120814 hom. )

Consequence

IL36RN
NM_012275.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.147

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-113059363-C-G is Benign according to our data. Variant chr2-113059363-C-G is described in ClinVar as [Benign]. Clinvar id is 2628158.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3 link	c.-27-49C>G	intron_variant	Intron 1 of 4	ENST00000393200.7	NP_036407.1	Q9UBH0A0A024R518
IL36RN	NM_173170.1 link	c.-27-49C>G	intron_variant	Intron 1 of 4		NP_775262.1	Q9UBH0A0A024R518
IL36RN	XM_047443918.1 link	c.-27-49C>G	intron_variant	Intron 2 of 5		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL36RN	ENST00000393200.7 link	c.-27-49C>G	intron_variant	Intron 1 of 4	1	NM_012275.3	ENSP00000376896.2	Q9UBH0
IL36RN	ENST00000346807.7 link	c.-27-49C>G	intron_variant	Intron 1 of 4	1		ENSP00000259212.3	Q9UBH0
IL36RN	ENST00000437409.2 link	c.-76C>G	upstream_gene_variant		1		ENSP00000409262.2	Q9UBH0C9JTH1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52076

AN:

151662

Hom.:

9722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.409

AC:

567762

AN:

1386716

Hom.:

120814

Cov.:

AF XY:

0.416

AC XY:

288278

AN XY:

693620

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.580

Gnomad4 FIN exome

AF:

0.448

Gnomad4 NFE exome

AF:

0.414

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.343

AC:

52113

AN:

151780

Hom.:

9730

Cov.:

AF XY:

0.348

AC XY:

25789

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.248

Hom.:

628

Bravo

AF:

0.322

Asia WGS

AF:

0.371

AC:

1290

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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