2-113059365-A-C

Variant names:

• chr2-113059365-A-C
• rs2278717
• NM_012275.3:c.-27-47A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012275.3(IL36RN):​c.-27-47A>C 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 1,547,278 control chromosomes in the GnomAD database, including 131,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9729 hom., cov: 32)
  • Exomes 𝑓: 0.41 (121412 hom.)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.746

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-113059365-A-C is Benign according to our data. Variant chr2-113059365-A-C is described in ClinVar as [Benign]. Clinvar id is 2628159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36RN	NM_012275.3	c.-27-47A>C		intron_variant	Intron 1 of 4	ENST00000393200.7	NP_036407.1
IL36RN	NM_173170.1	c.-27-47A>C		intron_variant	Intron 1 of 4		NP_775262.1
IL36RN	XM_047443918.1	c.-27-47A>C		intron_variant	Intron 2 of 5		XP_047299874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36RN	ENST00000393200.7	c.-27-47A>C		intron_variant	Intron 1 of 4	1	NM_012275.3	ENSP00000376896.2
IL36RN	ENST00000346807.7	c.-27-47A>C		intron_variant	Intron 1 of 4	1		ENSP00000259212.3
IL36RN	ENST00000437409.2	c.-74A>C		upstream_gene_variant		1		ENSP00000409262.2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52075 AN: 151668 Hom.: 9721 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.173

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: 570788 AN: 1395490 Hom.: 121412 Cov.: 22 AF XY: 0.415 AC XY: 289711 AN XY: 697712

Gnomad4 AFR exome AF: 0.179

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: 52112 AN: 151788 Hom.: 9729 Cov.: 32 AF XY: 0.348 AC XY: 25789 AN XY: 74192

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.359

Alfa AF: 0.396 Hom.: 11341

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

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	4.7
DANN	Benign	0.44

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: rs2278717; hg19: chr2-113816942; COSMIC: COSV61010335; COSMIC: COSV61010335;