2-113132727-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173842.3(IL1RN):c.390T>C(p.Ser130Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,614,016 control chromosomes in the GnomAD database, including 77,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9538 hom., cov: 33)

Exomes 𝑓: 0.29 ( 67767 hom. )

Consequence

IL1RN
NM_173842.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.15

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-113132727-T-C is Benign according to our data. Variant chr2-113132727-T-C is described in ClinVar as [Benign]. Clinvar id is 330827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3 link	c.390T>C	p.Ser130Ser	synonymous_variant	Exon 4 of 4	ENST00000409930.4	NP_776214.1	P18510-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4 link	c.390T>C	p.Ser130Ser	synonymous_variant	Exon 4 of 4	1	NM_173842.3	ENSP00000387173.3		P18510-1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51496

AN:

152098

Hom.:

9523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.305

AC:

76749

AN:

251324

Hom.:

13280

AF XY:

0.294

AC XY:

39936

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.593

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.294

AC:

430010

AN:

1461800

Hom.:

67767

Cov.:

AF XY:

0.289

AC XY:

210490

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.619

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.339

AC:

51534

AN:

152216

Hom.:

9538

Cov.:

AF XY:

0.339

AC XY:

25261

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.433

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.588

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.417

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.296

Hom.:

17950

Bravo

AF:

0.334

Asia WGS

AF:

0.347

AC:

1206

AN:

3478

EpiCase

AF:

0.277

EpiControl

AF:

0.274

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sterile multifocal osteomyelitis with periostitis and pustulosis

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over