dbSNP rs2637988: IL1RN:c.11-864G>A (chr2-113119202-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_173841.3(IL1RN):c.11-864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,050 control chromosomes in the GnomAD database, including 22,037 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 0.53 ( 22037 hom., cov: 32)

Consequence

IL1RN
NM_173841.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0830

Publications

41 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 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.11-864G>A	intron	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.10+1174G>A	intron	N/A	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-272-864G>A	intron	N/A	NP_001305843.1	P18510-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1RN	ENST00000259206.9	TSL:1	c.11-864G>A	intron	N/A	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.10+1174G>A	intron	N/A	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7	TSL:1	c.-210+1174G>A	intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81061

AN:

151934

Hom.:

22027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.533

AC:

81112

AN:

152050

Hom.:

22037

Cov.:

AF XY:

0.528

AC XY:

39225

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.441

AC:

18291

AN:

41462

American (AMR)

AF:

0.547

AC:

8363

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2071

AN:

3468

East Asian (EAS)

AF:

0.410

AC:

2121

AN:

5172

South Asian (SAS)

AF:

0.556

AC:

2679

AN:

4822

European-Finnish (FIN)

AF:

0.448

AC:

4732

AN:

10552

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.603

AC:

40967

AN:

67972

Other (OTH)

AF:

0.551

AC:

1164

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1933

3866

5799

7732

9665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.581

Hom.:

17699

Bravo

AF:

0.536

Asia WGS

AF:

0.482

AC:

1677

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

(source)

DANN

Benign

0.58

PhyloP100

-0.083

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over