Genetic Variant IL1RN:c.73+2028G>A (chr2-113122156-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.73+2028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,212 control chromosomes in the GnomAD database, including 4,241 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 ( 4241 hom., cov: 33)

Consequence

IL1RN
NM_173841.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0790

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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 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.73+2028G>A	intron	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.10+4128G>A	intron	N/A	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-39+538G>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.73+2028G>A	intron	N/A	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.10+4128G>A	intron	N/A	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7	TSL:1	c.-39+538G>A	intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32172

AN:

152094

Hom.:

4235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.0776

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.234

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

GnomAD4 genome

AF:

0.211

AC:

32185

AN:

152212

Hom.:

4241

Cov.:

AF XY:

0.214

AC XY:

15912

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0556

AC:

2309

AN:

41540

American (AMR)

AF:

0.283

AC:

4323

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1009

AN:

3472

East Asian (EAS)

AF:

0.0770

AC:

399

AN:

5184

South Asian (SAS)

AF:

0.281

AC:

1358

AN:

4828

European-Finnish (FIN)

AF:

0.306

AC:

3237

AN:

10590

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18763

AN:

67992

Other (OTH)

AF:

0.236

AC:

498

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1260

2520

3781

5041

6301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.231

Hom.:

1460

Bravo

AF:

0.201

Asia WGS

AF:

0.188

AC:

655

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.8

(source)

DANN

Benign

0.75

PhyloP100

0.079

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