2-113117988-A-G

Position:

• chr2-113117988-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000259206.9(IL1RN):​c.-31A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,357,394 control chromosomes in the GnomAD database, including 43,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4081 hom., cov: 33)
  • Exomes 𝑓: 0.25 (39308 hom.)
• Consequence: IL1RN ENST00000259206.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.25

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=-0.86).
• BP6: Variant 2-113117988-A-G is Benign according to our data. Variant chr2-113117988-A-G is described in ClinVar as [Benign]. Clinvar id is 330820.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/exons	MANE	UniProt
IL1RN	NM_000577.5	c.-31A>G		5_prime_UTR_variant	1/5
IL1RN	NM_001318914.2	c.-313A>G		5_prime_UTR_variant	1/7
IL1RN	NM_173841.3	c.-31A>G		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1RN	ENST00000259206.9	c.-31A>G		5_prime_UTR_variant	1/6	1
IL1RN	ENST00000354115.6	c.-31A>G		5_prime_UTR_variant	1/5	1		A1
IL1RN	ENST00000361779.7	c.-250A>G		5_prime_UTR_variant	1/6	1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31808 AN: 152080 Hom.: 4074 Cov.: 33

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.253 AC: 63655 AN: 251438 Hom.: 9027 AF XY: 0.256 AC XY: 34800 AN XY: 135900

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.0923

Gnomad SAS exome AF: 0.281

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.248 AC: 299099 AN: 1205194 Hom.: 39308 Cov.: 17 AF XY: 0.249 AC XY: 152795 AN XY: 612620

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.0828

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.209 AC: 31825 AN: 152200 Hom.: 4081 Cov.: 33 AF XY: 0.212 AC XY: 15779 AN XY: 74394

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.232

Alfa AF: 0.257 Hom.: 4814

Bravo AF: 0.199

Asia WGS AF: 0.195 AC: 679 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	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. 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	-0.86
CADD	Benign	0.39
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234678; hg19: chr2-113875565; COSMIC: COSV52080796; COSMIC: COSV52080796;