rs419598

Positions:

chr2-113129630-T-C

Variant summary

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

The NM_173842.3(IL1RN):c.171T>C(p.Ala57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,609,674 control chromosomes in the GnomAD database, including 59,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4288 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55095 hom. )

Consequence

IL1RN
NM_173842.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.00

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=-0.58).

BP6

Variant 2-113129630-T-C is Benign according to our data. Variant chr2-113129630-T-C is described in ClinVar as [Benign]. Clinvar id is 330825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113129630-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1RN	NM_173842.3 linkuse as main transcript	c.171T>C	p.Ala57=	synonymous_variant	2/4	ENST00000409930.4	NP_776214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409930.4 linkuse as main transcript	c.171T>C	p.Ala57=	synonymous_variant	2/4	1	NM_173842.3	ENSP00000387173	P4	P18510-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32829

AN:

152038

Hom.:

4280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0777

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.239

GnomAD3 exomes

AF:

0.256

AC:

64470

AN:

251432

Hom.:

9252

AF XY:

0.259

AC XY:

35246

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.297

Gnomad EAS exome

AF:

0.0708

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.268

AC:

390790

AN:

1457516

Hom.:

55095

Cov.:

AF XY:

0.268

AC XY:

194275

AN XY:

725298

show subpopulations

Gnomad4 AFR exome

AF:

0.0625

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.289

Gnomad4 EAS exome

AF:

0.0600

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.216

AC:

32867

AN:

152158

Hom.:

4288

Cov.:

AF XY:

0.219

AC XY:

16273

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.0771

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.264

Hom.:

9069

Bravo

AF:

0.206

Asia WGS

AF:

0.196

AC:

683

AN:

3478

EpiCase

AF:

0.272

EpiControl

AF:

0.268

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -
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: Variant associated with alopecia, ankylosing spondylitis, hypertension in pregnancy, carotid atherosclerosis - dubious and not relevant to patient disease -

Sterile multifocal osteomyelitis with periostitis and pustulosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 17899305, 8641687, 19818512, 12624309, 11841485) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.3

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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