chr2-113059604-C-T

Position:

• chr2-113059604-C-T

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.29+137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 949,194 control chromosomes in the GnomAD database, including 215,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36722 hom., cov: 30)
  • Exomes 𝑓: 0.66 (179070 hom.)
• Consequence: IL36RN NM_012275.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.393

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=-0.81).
• BP6: Variant 2-113059604-C-T is Benign according to our data. Variant chr2-113059604-C-T is described in ClinVar as [Benign]. Clinvar id is 2628183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL36RN	NM_012275.3	c.29+137C>T		intron_variant		ENST00000393200.7
IL36RN	NM_173170.1	c.29+137C>T		intron_variant
IL36RN	XM_047443918.1	c.29+137C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL36RN	ENST00000393200.7	c.29+137C>T		intron_variant		1	NM_012275.3	P1
IL36RN	ENST00000346807.7	c.29+137C>T		intron_variant		1		P1
IL36RN	ENST00000437409.2	c.29+137C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104405 AN: 151844 Hom.: 36669 Cov.: 30

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.660 AC: 526178 AN: 797232 Hom.: 179070 AF XY: 0.669 AC XY: 278938 AN XY: 417136

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.888

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.688 AC: 104510 AN: 151962 Hom.: 36722 Cov.: 30 AF XY: 0.693 AC XY: 51434 AN XY: 74260

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.711

Alfa AF: 0.626 Hom.: 3746

Bravo AF: 0.696

Asia WGS AF: 0.913 AC: 3173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.66

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: rs2515392; hg19: chr2-113817181;