Genetic Variant IL1RN:n.-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 ENST00000409052.6(IL1RN):n.-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
ENST00000409052.6 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: 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=-0.91).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
IL1RN	XM_011511121.2 link	c.-272-2562C>T	intron_variant	Intron 3 of 8	XP_011509423.1
IL1RN	XM_047444184.1 link	c.-272-2562C>T	intron_variant	Intron 4 of 9	XP_047300140.1
IL1RN	XM_047444185.1 link	c.-401-33C>T	intron_variant	Intron 3 of 9	XP_047300141.1
IL1RN	XM_047444186.1 link	c.-209-3944C>T	intron_variant	Intron 3 of 7	XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1RN	ENST00000409052.6 link	n.-272-2562C>T		intron_variant	Intron 3 of 9	5		ENSP00000387210.1
IL1RN	ENST00000465812.6 link	n.647-33C>T		intron_variant	Intron 4 of 5	5

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over