Genetic Variant IL1RN:c.205+431A>G (chr2-113130095-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173842.3(IL1RN):c.205+431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 193,634 control chromosomes in the GnomAD database, including 5,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4290 hom., cov: 32)

Exomes 𝑓: 0.20 ( 932 hom. )

Consequence

IL1RN
NM_173842.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1RN	NM_173842.3 link	c.205+431A>G		intron_variant	Intron 2 of 3	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.205+431A>G		intron_variant	Intron 2 of 3	1	NM_173842.3	ENSP00000387173.3		P18510-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32850

AN:

152028

Hom.:

4282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.196

AC:

8150

AN:

41488

Hom.:

932

Cov.:

AF XY:

0.197

AC XY:

4255

AN XY:

21560

show subpopulations

African (AFR)

AF:

0.0434

AC:

105

AN:

2422

American (AMR)

AF:

0.293

AC:

1063

AN:

3624

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

184

AN:

900

East Asian (EAS)

AF:

0.0520

AC:

179

AN:

3444

South Asian (SAS)

AF:

0.213

AC:

1036

AN:

4858

European-Finnish (FIN)

AF:

0.219

AC:

219

AN:

1002

Middle Eastern (MID)

AF:

0.179

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.215

AC:

4964

AN:

23120

Other (OTH)

AF:

0.190

AC:

371

AN:

1956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

280

560

841

1121

1401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.216

AC:

32888

AN:

152146

Hom.:

4290

Cov.:

AF XY:

0.219

AC XY:

16279

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0709

AC:

2944

AN:

41532

American (AMR)

AF:

0.284

AC:

4339

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1010

AN:

3468

East Asian (EAS)

AF:

0.0772

AC:

400

AN:

5184

South Asian (SAS)

AF:

0.289

AC:

1392

AN:

4822

European-Finnish (FIN)

AF:

0.305

AC:

3224

AN:

10564

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18788

AN:

67976

Other (OTH)

AF:

0.238

AC:

502

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1282

2564

3845

5127

6409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.180

Hom.:

613

Bravo

AF:

0.206

Asia WGS

AF:

0.196

AC:

683

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

(source)

DANN

Benign

0.46

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

Other links and lift over