dbSNP rs2234679: IL1RN:c.-12G>C (chr2-113118007-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173841.3(IL1RN):c.-12G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,519,538 control chromosomes in the GnomAD database, including 50,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4082 hom., cov: 33)

Exomes 𝑓: 0.25 ( 46386 hom. )

Consequence

IL1RN
NM_173841.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.323

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-113118007-G-C is Benign according to our data. Variant chr2-113118007-G-C is described in ClinVar as Benign. ClinVar VariationId is 330821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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: NM_173841.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	NM_173841.3	c.-12G>C	5_prime_UTR	Exon 1 of 6	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.-12G>C	5_prime_UTR	Exon 1 of 5	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-294G>C	5_prime_UTR	Exon 1 of 7	NP_001305843.1	P18510-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	ENST00000259206.9	TSL:1	c.-12G>C	5_prime_UTR	Exon 1 of 6	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.-12G>C	5_prime_UTR	Exon 1 of 5	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7	TSL:1	c.-231G>C	5_prime_UTR	Exon 1 of 6	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31816

AN:

152078

Hom.:

4075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.0973

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.253

AC:

63662

AN:

251438

AF XY:

0.256

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.0924

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.253

AC:

345495

AN:

1367340

Hom.:

46386

Cov.:

AF XY:

0.254

AC XY:

173843

AN XY:

685680

show subpopulations

African (AFR)

AF:

0.0455

AC:

1465

AN:

32178

American (AMR)

AF:

0.315

AC:

14041

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7319

AN:

25506

East Asian (EAS)

AF:

0.0828

AC:

3256

AN:

39320

South Asian (SAS)

AF:

0.275

AC:

23141

AN:

84262

European-Finnish (FIN)

AF:

0.296

AC:

15758

AN:

53216

Middle Eastern (MID)

AF:

0.212

AC:

1187

AN:

5590

European-Non Finnish (NFE)

AF:

0.259

AC:

265421

AN:

1025598

Other (OTH)

AF:

0.243

AC:

13907

AN:

57118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

12647

25294

37942

50589

63236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8456

16912

25368

33824

42280

<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:

31833

AN:

152198

Hom.:

4082

Cov.:

AF XY:

0.212

AC XY:

15787

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0582

AC:

2419

AN:

41562

American (AMR)

AF:

0.278

AC:

4249

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3470

East Asian (EAS)

AF:

0.0968

AC:

502

AN:

5186

South Asian (SAS)

AF:

0.283

AC:

1363

AN:

4810

European-Finnish (FIN)

AF:

0.304

AC:

3222

AN:

10586

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18285

AN:

67984

Other (OTH)

AF:

0.232

AC:

489

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1268

2536

3803

5071

6339

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:

0.246

Hom.:

1014

Bravo

AF:

0.199

Asia WGS

AF:

0.195

AC:

679

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Sterile multifocal osteomyelitis with periostitis and pustulosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.0

(source)

DANN

Benign

0.80

PhyloP100

-0.32

PromoterAI

-0.050

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