chr2-113132802-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_173842.3(IL1RN):c.465C>T(p.Pro155Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,614,240 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 5 hom. )

Consequence

IL1RN
NM_173842.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.28

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-113132802-C-T is Benign according to our data. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113132802-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 537716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00398 (606/152356) while in subpopulation AFR AF = 0.0136 (564/41590). AF 95% confidence interval is 0.0126. There are 6 homozygotes in GnomAd4. There are 299 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3 link	c.465C>T	p.Pro155Pro	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.465C>T	p.Pro155Pro	synonymous_variant	Exon 4 of 4	1	NM_173842.3	ENSP00000387173.3		P18510-1

Frequencies

GnomAD3 genomes

AF:

0.00397

AC:

604

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00112

AC:

282

AN:

251368

AF XY:

0.000861

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000446

AC:

652

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

283

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0162

AC:

544

AN:

33478

American (AMR)

AF:

0.000827

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1112006

Other (OTH)

AF:

0.000844

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

128

171

214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00398

AC:

606

AN:

152356

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

299

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0136

AC:

564

AN:

41590

American (AMR)

AF:

0.00183

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00167

Hom.:

Bravo

AF:

0.00494

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sterile multifocal osteomyelitis with periostitis and pustulosis

Benign:2

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IL1RN: BP4, BP7, BS1 -

Autoinflammatory syndrome

Benign:1

Feb 08, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.67

(source)

DANN

Benign

0.56

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism

(source)

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

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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