rs315951

Variant names:

• chr2-113133009-C-G
• rs315951
• NM_173842.3:c.*138C>G

Variant summary

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

The NM_173842.3(IL1RN):​c.*138C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 787,330 control chromosomes in the GnomAD database, including 42,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9445 hom., cov: 33)
  • Exomes 𝑓: 0.30 (33041 hom.)
• Consequence: IL1RN NM_173842.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.610
• Publications: 52 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=-0.92).
• BP6: Variant 2-113133009-C-G is Benign according to our data. Variant chr2-113133009-C-G is described in ClinVar as Benign. ClinVar VariationId is 330832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.*138C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.*138C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_173842.3	ENSP00000387173.3

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51270 AN: 152048 Hom.: 9431 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.304 AC: 193077 AN: 635164 Hom.: 33041 Cov.: 8 AF XY: 0.295 AC XY: 100465 AN XY: 340110

African (AFR) AF: 0.426 AC: 7288 AN: 17116

American (AMR) AF: 0.239 AC: 8368 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 4230 AN: 20276

East Asian (EAS) AF: 0.644 AC: 21027 AN: 32670

South Asian (SAS) AF: 0.145 AC: 9435 AN: 65018

European-Finnish (FIN) AF: 0.419 AC: 18184 AN: 43356

Middle Eastern (MID) AF: 0.206 AC: 569 AN: 2764

European-Non Finnish (NFE) AF: 0.295 AC: 113977 AN: 385926

Other (OTH) AF: 0.303 AC: 9999 AN: 33004

GnomAD4 genome AF: 0.337 AC: 51306 AN: 152166 Hom.: 9445 Cov.: 33 AF XY: 0.338 AC XY: 25155 AN XY: 74392

African (AFR) AF: 0.424 AC: 17603 AN: 41524

American (AMR) AF: 0.235 AC: 3600 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.607 AC: 3136 AN: 5164

South Asian (SAS) AF: 0.145 AC: 698 AN: 4822

European-Finnish (FIN) AF: 0.417 AC: 4413 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20174 AN: 67984

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.331 Hom.: 1285

Bravo AF: 0.332

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

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 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1

Jan 13, 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	-0.92
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs315951; hg19: chr2-113890586;