dbSNP rs447713: 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

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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