rs878972

Positions:

chr2-113120136-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000259206.9(IL1RN):c.73+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,604,640 control chromosomes in the GnomAD database, including 56,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4070 hom., cov: 30)

Exomes 𝑓: 0.26 ( 52548 hom. )

Consequence

IL1RN
ENST00000259206.9 splice_region, intron

Scores

Splicing: ADA: 0.00002619

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.149

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 2-113120136-A-C is Benign according to our data. Variant chr2-113120136-A-C is described in ClinVar as [Benign]. Clinvar id is 330822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113120136-A-C is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
IL1RN	NM_000577.5 linkuse as main transcript	c.10+2108A>C	intron_variant	NP_000568.1
IL1RN	NM_001318914.2 linkuse as main transcript	c.-210+8A>C	splice_region_variant, intron_variant	NP_001305843.1
IL1RN	NM_173841.3 linkuse as main transcript	c.73+8A>C	splice_region_variant, intron_variant	NP_776213.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris	UniProt
IL1RN	ENST00000259206.9 linkuse as main transcript	c.73+8A>C	splice_region_variant, intron_variant	1	ENSP00000259206		P18510-3
IL1RN	ENST00000354115.6 linkuse as main transcript	c.10+2108A>C	intron_variant	1	ENSP00000329072	A1	P18510-2
IL1RN	ENST00000361779.7 linkuse as main transcript	c.-209-1312A>C	intron_variant	1	ENSP00000354816		P18510-4

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31746

AN:

151264

Hom.:

4064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.253

AC:

63662

AN:

251238

Hom.:

9001

AF XY:

0.256

AC XY:

34830

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0536

Gnomad AMR exome

AF:

0.317

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.0945

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.263

AC:

382285

AN:

1453256

Hom.:

52548

Cov.:

AF XY:

0.263

AC XY:

190375

AN XY:

723634

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.210

AC:

31763

AN:

151384

Hom.:

4070

Cov.:

AF XY:

0.212

AC XY:

15694

AN XY:

73864

show subpopulations

Gnomad4 AFR

AF:

0.0609

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.238

Hom.:

2183

Bravo

AF:

0.199

Asia WGS

AF:

0.202

AC:

703

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Sterile multifocal osteomyelitis with periostitis and pustulosis

Benign:2

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. -
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 12, 2021	- -
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

-0.93

CADD

Benign

5.0

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

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