rs2234677

Variant names:

• chr2-113117932-G-A
• rs2234677
• ENST00000259206.9:c.-87G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-113117932-G-A
• chr2-113117932-G-C
• chr2-113117932-G-T

Variant summary

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

The ENST00000259206.9(IL1RN):​c.-87G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 837,914 control chromosomes in the GnomAD database, including 27,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4092 hom., cov: 32)
  • Exomes 𝑓: 0.25 (23107 hom.)
• Consequence: IL1RN ENST00000259206.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.267
• Publications: 23 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=-0.84).
• BP6: Variant 2-113117932-G-A is Benign according to our data. Variant chr2-113117932-G-A is described in ClinVar as Benign. ClinVar VariationId is 330817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	XM_011511121.2	c.-272-2134G>A		intron_variant	Intron 3 of 8		XP_011509423.1
IL1RN	XM_047444184.1	c.-272-2134G>A		intron_variant	Intron 4 of 9		XP_047300140.1
IL1RN	XM_047444185.1	c.-273+267G>A		intron_variant	Intron 4 of 9		XP_047300141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000259206.9	c.-87G>A		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000259206.5
IL1RN	ENST00000354115.6	c.-87G>A		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000329072.3
IL1RN	ENST00000361779.7	c.-306G>A		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000354816.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31815 AN: 152044 Hom.: 4086 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.249 AC: 170672 AN: 685750 Hom.: 23107 Cov.: 9 AF XY: 0.250 AC XY: 92648 AN XY: 370026

African (AFR) AF: 0.0530 AC: 1000 AN: 18864

American (AMR) AF: 0.315 AC: 13791 AN: 43728

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6197 AN: 21322

East Asian (EAS) AF: 0.0821 AC: 2984 AN: 36334

South Asian (SAS) AF: 0.274 AC: 19402 AN: 70790

European-Finnish (FIN) AF: 0.296 AC: 15655 AN: 52908

Middle Eastern (MID) AF: 0.214 AC: 710 AN: 3322

European-Non Finnish (NFE) AF: 0.254 AC: 102401 AN: 403622

Other (OTH) AF: 0.245 AC: 8532 AN: 34860

GnomAD4 genome AF: 0.209 AC: 31830 AN: 152164 Hom.: 4092 Cov.: 32 AF XY: 0.212 AC XY: 15784 AN XY: 74360

African (AFR) AF: 0.0580 AC: 2412 AN: 41554

American (AMR) AF: 0.278 AC: 4252 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.0967 AC: 502 AN: 5192

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4814

European-Finnish (FIN) AF: 0.305 AC: 3215 AN: 10554

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18287 AN: 67986

Other (OTH) AF: 0.233 AC: 492 AN: 2116

Alfa AF: 0.247 Hom.: 4681

Bravo AF: 0.199

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.69
PhyloP100		-0.27
PromoterAI		0.019	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2234677; hg19: chr2-113875509; COSMIC: COSV52079920; COSMIC: COSV52079920;