chr2-113133009-C-G

Position:

• chr2-113133009-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
IL1RN	NM_173842.3	c.*138C>G		3_prime_UTR_variant	4/4	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4	c.*138C>G		3_prime_UTR_variant	4/4	1	NM_173842.3	ENSP00000387173	P4

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

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.303

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

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.281

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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 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

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	-0.92
CADD	Benign	7.0
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs315951; hg19: chr2-113890586;