Genetic Variant IL1RN:c.11-230G>T (chr2-113119836-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_173841.3(IL1RN):c.11-230G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,092 control chromosomes in the GnomAD database, including 4,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 4107 hom., cov: 32)

Consequence

IL1RN
NM_173841.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.153

Publications

13 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-113119836-G-T is Benign according to our data. Variant chr2-113119836-G-T is described in ClinVar as Benign. ClinVar VariationId is 1232909.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 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.11-230G>T	intron	N/A	NP_776213.1	P18510-3
IL1RN	NM_000577.5	c.10+1808G>T	intron	N/A	NP_000568.1	P18510-2
IL1RN	NM_001318914.2	c.-272-230G>T	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.11-230G>T	intron	N/A	ENSP00000259206.5	P18510-3
IL1RN	ENST00000354115.6	TSL:1	c.10+1808G>T	intron	N/A	ENSP00000329072.3	P18510-2
IL1RN	ENST00000361779.7	TSL:1	c.-209-1612G>T	intron	N/A	ENSP00000354816.3	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31888

AN:

151974

Hom.:

4101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.0971

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.229

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

GnomAD4 genome

AF:

0.210

AC:

31904

AN:

152092

Hom.:

4107

Cov.:

AF XY:

0.212

AC XY:

15791

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0607

AC:

2521

AN:

41512

American (AMR)

AF:

0.275

AC:

4208

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

993

AN:

3468

East Asian (EAS)

AF:

0.0966

AC:

500

AN:

5176

South Asian (SAS)

AF:

0.287

AC:

1380

AN:

4816

European-Finnish (FIN)

AF:

0.305

AC:

3221

AN:

10552

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18307

AN:

67976

Other (OTH)

AF:

0.231

AC:

487

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1229

2458

3688

4917

6146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.253

Hom.:

6681

Bravo

AF:

0.199

Asia WGS

AF:

0.197

AC:

684

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.5

(source)

DANN

Benign

0.78

PhyloP100

0.15

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