dbSNP rs17042917: IL1RN:n.-301G>A (chr2-113113086-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 ENST00000409052.6(IL1RN):n.-301G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,146 control chromosomes in the GnomAD database, including 1,626 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 0.14 ( 1626 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL1RN
ENST00000409052.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

Publications

9 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL1RN	XM_011511121.2 link	c.-301G>A	5_prime_UTR_variant	Exon 3 of 9	XP_011509423.1	P18510-4A0A024R528
IL1RN	XM_047444184.1 link	c.-301G>A	5_prime_UTR_variant	Exon 4 of 10	XP_047300140.1
IL1RN	XM_047444185.1 link	c.-430G>A	5_prime_UTR_variant	Exon 3 of 10	XP_047300141.1
IL1RN	XM_047444186.1 link	c.-238G>A	5_prime_UTR_variant	Exon 3 of 8	XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL1RN	ENST00000409052.6 link	n.-301G>A	non_coding_transcript_exon_variant	Exon 3 of 10	5	ENSP00000387210.1	P18510-4
IL1RN	ENST00000463073.6 link	n.274G>A	non_coding_transcript_exon_variant	Exon 3 of 4	5
IL1RN	ENST00000465812.6 link	n.618G>A	non_coding_transcript_exon_variant	Exon 4 of 6	5
IL1RN	ENST00000409052.6 link	n.-301G>A	5_prime_UTR_variant	Exon 3 of 10	5	ENSP00000387210.1	P18510-4

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21151

AN:

152028

Hom.:

1632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.115

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.139

AC:

21157

AN:

152146

Hom.:

1626

Cov.:

AF XY:

0.142

AC XY:

10567

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.170

AC:

7055

AN:

41500

American (AMR)

AF:

0.164

AC:

2503

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0663

AC:

230

AN:

3470

East Asian (EAS)

AF:

0.272

AC:

1405

AN:

5164

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4826

European-Finnish (FIN)

AF:

0.168

AC:

1774

AN:

10558

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7233

AN:

68012

Other (OTH)

AF:

0.114

AC:

241

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

925

1851

2776

3702

4627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.105

Hom.:

1154

Bravo

AF:

0.140

Asia WGS

AF:

0.182

AC:

631

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.66

PhyloP100

-0.22

Mutation Taster

=296/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over