ENST00000472292.1:n.496C>T

Variant names:

• chr2-113129906-C-T
• rs2071459
• ENST00000472292.1:n.496C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000472292.1(IL1RN):​n.496C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 504,864 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3103 hom., cov: 32)
  • Exomes 𝑓: 0.17 (8222 hom.)
• Consequence: IL1RN ENST00000472292.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.604
• Publications: 4 publications found

Genes affected

IL1RN (HGNC:6000): (interleukin 1 receptor antagonist) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses, particularly in the acute phase of infection and inflammation. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

IL1RN Gene-Disease associations (from GenCC):

• sterile multifocal osteomyelitis with periostitis and pustulosis

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-113129906-C-T is Benign according to our data. Variant chr2-113129906-C-T is described in ClinVar as Benign. ClinVar VariationId is 537717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.205+242C>T		intron_variant	Intron 2 of 3	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.205+242C>T		intron_variant	Intron 2 of 3	1	NM_173842.3	ENSP00000387173.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27265 AN: 151948 Hom.: 3106 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.174 AC: 61385 AN: 352798 Hom.: 8222 Cov.: 0 AF XY: 0.170 AC XY: 31733 AN XY: 187084

African (AFR) AF: 0.224 AC: 2316 AN: 10354

American (AMR) AF: 0.154 AC: 2473 AN: 16060

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 1202 AN: 10556

East Asian (EAS) AF: 0.624 AC: 14799 AN: 23720

South Asian (SAS) AF: 0.117 AC: 5075 AN: 43382

European-Finnish (FIN) AF: 0.250 AC: 5136 AN: 20528

Middle Eastern (MID) AF: 0.134 AC: 199 AN: 1480

European-Non Finnish (NFE) AF: 0.130 AC: 26861 AN: 206622

Other (OTH) AF: 0.165 AC: 3324 AN: 20096

GnomAD4 genome AF: 0.179 AC: 27269 AN: 152066 Hom.: 3103 Cov.: 32 AF XY: 0.184 AC XY: 13709 AN XY: 74312

African (AFR) AF: 0.223 AC: 9255 AN: 41458

American (AMR) AF: 0.144 AC: 2202 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3468

East Asian (EAS) AF: 0.582 AC: 2995 AN: 5150

South Asian (SAS) AF: 0.119 AC: 574 AN: 4814

European-Finnish (FIN) AF: 0.247 AC: 2611 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8704 AN: 67980

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.161 Hom.: 308

Bravo AF: 0.179

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23462747, 27884173) -

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

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	-0.82
CADD	Benign	8.4
DANN	Benign	0.72
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071459; hg19: chr2-113887483;