rs878972

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

sterile multifocal osteomyelitis with periostitis and pustulosis
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

IL1RN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 330822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL1RN	NM_173841.3 link	c.73+8A>C	splice_region_variant, intron_variant	Intron 2 of 5	NP_776213.1	P18510-3
IL1RN	NM_000577.5 link	c.10+2108A>C	intron_variant	Intron 1 of 4	NP_000568.1	P18510-2
IL1RN	NM_001318914.2 link	c.-210+8A>C	splice_region_variant, intron_variant	Intron 2 of 6	NP_001305843.1	P18510-4A0A024R528

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL1RN	ENST00000259206.9 link	c.73+8A>C	splice_region_variant, intron_variant	Intron 2 of 5	1	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6 link	c.10+2108A>C	intron_variant	Intron 1 of 4	1	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7 link	c.-209-1312A>C	intron_variant	Intron 1 of 5	1	ENSP00000354816.3	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

GnomAD2 exomes

AF:

0.253

AC:

63662

AN:

251238

AF XY:

0.256

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 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

African (AFR)

AF:

0.0499

AC:

1664

AN:

33340

American (AMR)

AF:

0.313

AC:

13981

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7472

AN:

26076

East Asian (EAS)

AF:

0.101

AC:

3990

AN:

39668

South Asian (SAS)

AF:

0.282

AC:

24268

AN:

86086

European-Finnish (FIN)

AF:

0.298

AC:

15917

AN:

53408

Middle Eastern (MID)

AF:

0.218

AC:

1244

AN:

5696

European-Non Finnish (NFE)

AF:

0.270

AC:

298606

AN:

1104170

Other (OTH)

AF:

0.252

AC:

15143

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

13059

26119

39178

52238

65297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9890

19780

29670

39560

49450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

31763

AN:

151384

Hom.:

4070

Cov.:

AF XY:

0.212

AC XY:

15694

AN XY:

73864

show subpopulations

African (AFR)

AF:

0.0609

AC:

2512

AN:

41244

American (AMR)

AF:

0.275

AC:

4172

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

994

AN:

3470

East Asian (EAS)

AF:

0.104

AC:

540

AN:

5174

South Asian (SAS)

AF:

0.288

AC:

1376

AN:

4772

European-Finnish (FIN)

AF:

0.303

AC:

3157

AN:

10404

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18242

AN:

67856

Other (OTH)

AF:

0.231

AC:

485

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1174

2347

3521

4694

5868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.239

Hom.:

2870

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sterile multifocal osteomyelitis with periostitis and pustulosis

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.0

(source)

DANN

Benign

0.37

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over