dbSNP rs17207494: IL1RN:n.-471-4683A>C (chr2-113106433-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000409052.6(IL1RN):n.-471-4683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,146 control chromosomes in the GnomAD database, including 8,356 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 0.32 ( 8356 hom., cov: 33)

Consequence

IL1RN
ENST00000409052.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.343

Publications

6 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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

IL1RN links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL1RN	XM_011511121.2 link	c.-471-4683A>C	intron_variant	Intron 1 of 8	XP_011509423.1	P18510-4A0A024R528
IL1RN	XM_047444184.1 link	c.-643-781A>C	intron_variant	Intron 1 of 9	XP_047300140.1
IL1RN	XM_047444185.1 link	c.-600-4683A>C	intron_variant	Intron 1 of 9	XP_047300141.1
IL1RN	XM_047444186.1 link	c.-408-4683A>C	intron_variant	Intron 1 of 7	XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL1RN	ENST00000409052.6 link	n.-471-4683A>C	intron_variant	Intron 1 of 9	5	ENSP00000387210.1	P18510-4
IL1RN	ENST00000463073.6 link	n.104-4683A>C	intron_variant	Intron 1 of 3	5
IL1RN	ENST00000465812.6 link	n.276-781A>C	intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48467

AN:

152028

Hom.:

8350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.352

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

GnomAD4 genome

AF:

0.319

AC:

48491

AN:

152146

Hom.:

8356

Cov.:

AF XY:

0.314

AC XY:

23310

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.232

AC:

9629

AN:

41510

American (AMR)

AF:

0.321

AC:

4900

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1350

AN:

3470

East Asian (EAS)

AF:

0.0672

AC:

349

AN:

5192

South Asian (SAS)

AF:

0.347

AC:

1669

AN:

4804

European-Finnish (FIN)

AF:

0.299

AC:

3163

AN:

10580

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26067

AN:

67990

Other (OTH)

AF:

0.355

AC:

747

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1696

3392

5087

6783

8479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.334

Hom.:

1113

Bravo

AF:

0.318

Asia WGS

AF:

0.257

AC:

892

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.61

(source)

DANN

Benign

0.67

PhyloP100

-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over