rs9005

chr2-113133835-G-A

Variant summary

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

The NM_173842.3(IL1RN):c.*964G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,686 control chromosomes in the GnomAD database, including 6,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6831 hom., cov: 32)
  • Exomes 𝑓: 0.29 (23 hom.)
• Consequence: IL1RN NM_173842.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.282

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-113133835-G-A is Benign according to our data. Variant chr2-113133835-G-A is described in ClinVar as [Benign]. Clinvar id is 330845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1RN	NM_173842.3	c.*964G>A		3_prime_UTR_variant	4/4	ENST00000409930.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000409930.4	c.*964G>A		3_prime_UTR_variant	4/4	1	NM_173842.3	P4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43948 AN: 151910 Hom.: 6818 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.292 AC: 192 AN: 658 Hom.: 23 Cov.: 0 AF XY: 0.290 AC XY: 116 AN XY: 400

Gnomad4 AFR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.289 AC: 43987 AN: 152028 Hom.: 6831 Cov.: 32 AF XY: 0.293 AC XY: 21792 AN XY: 74288

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.311

Alfa AF: 0.304 Hom.: 11904

Bravo AF: 0.296

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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	-0.87
Cadd	Benign	2.7
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9005; hg19: chr2-113891412; COSMIC: COSV52082307; COSMIC: COSV52082307;