dbSNP rs2234676: IL1RN:c.-272-2215G>A (chr2-113117851-G-A) – 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 XM_011511121.2(IL1RN):c.-272-2215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 706,342 control chromosomes in the GnomAD database, including 22,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4092 hom., cov: 32)

Exomes 𝑓: 0.25 ( 18358 hom. )

Consequence

IL1RN
XM_011511121.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.968

Publications

8 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=-0.87).

BP6

Variant 2-113117851-G-A is Benign according to our data. Variant chr2-113117851-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	NM_173841.3	c.-168G>A	upstream_gene	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.-168G>A	upstream_gene	N/A	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-450G>A	upstream_gene	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	ENST00000409052.6	TSL:5	n.-272-2215G>A	intron	N/A	ENSP00000387210.1	P18510-4
IL1RN	ENST00000465812.6	TSL:5	n.775+186G>A	intron	N/A
IL1RN	ENST00000259206.9	TSL:1	c.-168G>A	upstream_gene	N/A	ENSP00000259206.5	P18510-3

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31821

AN:

152036

Hom.:

4086

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:

0.0971

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.247

AC:

137057

AN:

554188

Hom.:

18358

Cov.:

AF XY:

0.248

AC XY:

74147

AN XY:

299140

show subpopulations

African (AFR)

AF:

0.0536

AC:

840

AN:

15666

American (AMR)

AF:

0.301

AC:

9905

AN:

32894

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

4598

AN:

16386

East Asian (EAS)

AF:

0.0820

AC:

2905

AN:

35406

South Asian (SAS)

AF:

0.265

AC:

15540

AN:

58724

European-Finnish (FIN)

AF:

0.286

AC:

13206

AN:

46162

Middle Eastern (MID)

AF:

0.210

AC:

461

AN:

2192

European-Non Finnish (NFE)

AF:

0.260

AC:

82268

AN:

316964

Other (OTH)

AF:

0.246

AC:

7334

AN:

29794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

4200

8400

12599

16799

20999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

31836

AN:

152154

Hom.:

4092

Cov.:

AF XY:

0.212

AC XY:

15798

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0581

AC:

2415

AN:

41552

American (AMR)

AF:

0.278

AC:

4251

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1016

AN:

3468

East Asian (EAS)

AF:

0.0966

AC:

500

AN:

5176

South Asian (SAS)

AF:

0.284

AC:

1369

AN:

4818

European-Finnish (FIN)

AF:

0.305

AC:

3227

AN:

10580

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.269

AC:

18280

AN:

67960

Other (OTH)

AF:

0.233

AC:

492

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1237

2475

3712

4950

6187

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:

0.232

Hom.:

587

Bravo

AF:

0.199

Asia WGS

AF:

0.195

AC:

678

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.31

PhyloP100

-0.97

PromoterAI

0.0074

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