Genetic Variant IL1RN:c.-272-2562C>T (chr2-113117504-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_011511121.2(IL1RN):c.-272-2562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 164,572 control chromosomes in the GnomAD database, including 4,349 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 0.21 ( 4098 hom., cov: 33)

Exomes 𝑓: 0.18 ( 251 hom. )

Consequence

IL1RN
XM_011511121.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

3 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

IL1RN links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409052.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1RN	ENST00000409052.6	TSL:5	n.-272-2562C>T		intron	N/A	ENSP00000387210.1	P18510-4
	IL1RN	ENST00000465812.6	TSL:5	n.647-33C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31844

AN:

152102

Hom.:

4092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0584

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.0970

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.178

AC:

2200

AN:

12352

Hom.:

251

Cov.:

AF XY:

0.181

AC XY:

1167

AN XY:

6440

show subpopulations

African (AFR)

AF:

0.0452

AC:

AN:

310

American (AMR)

AF:

0.248

AC:

536

AN:

2160

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

AN:

194

East Asian (EAS)

AF:

0.0296

AC:

AN:

744

South Asian (SAS)

AF:

0.191

AC:

265

AN:

1384

European-Finnish (FIN)

AF:

0.120

AC:

AN:

184

Middle Eastern (MID)

AF:

0.0938

AC:

AN:

European-Non Finnish (NFE)

AF:

0.181

AC:

1231

AN:

6794

Other (OTH)

AF:

0.149

AC:

AN:

550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.209

AC:

31859

AN:

152220

Hom.:

4098

Cov.:

AF XY:

0.212

AC XY:

15804

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0582

AC:

2420

AN:

41556

American (AMR)

AF:

0.278

AC:

4255

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3470

East Asian (EAS)

AF:

0.0965

AC:

500

AN:

5184

South Asian (SAS)

AF:

0.284

AC:

1370

AN:

4824

European-Finnish (FIN)

AF:

0.305

AC:

3221

AN:

10572

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18298

AN:

68006

Other (OTH)

AF:

0.232

AC:

491

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1253

2506

3760

5013

6266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.221

Hom.:

1582

Bravo

AF:

0.199

Asia WGS

AF:

0.196

AC:

681

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.39

(source)

DANN

Benign

0.33

PhyloP100

-1.4

PromoterAI

-0.034

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over