dbSNP rs315920: IL1RN:n.-273+2327C>T (chr2-113115441-C-T) – 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.-273+2327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,166 control chromosomes in the GnomAD database, including 2,030 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 0.15 ( 2030 hom., cov: 31)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

IL1RN
ENST00000409052.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

19 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL1RN	XM_011511121.2 link	c.-273+2327C>T	intron_variant	Intron 3 of 8	XP_011509423.1	P18510-4A0A024R528
IL1RN	XM_047444184.1 link	c.-273+2327C>T	intron_variant	Intron 4 of 9	XP_047300140.1
IL1RN	XM_047444185.1 link	c.-401-2096C>T	intron_variant	Intron 3 of 9	XP_047300141.1
IL1RN	XM_047444186.1 link	c.-210+2327C>T	intron_variant	Intron 3 of 7	XP_047300142.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IL1RN	ENST00000409052.6 link	n.-273+2327C>T	intron_variant	Intron 3 of 9	5	ENSP00000387210.1	P18510-4
IL1RN	ENST00000463073.6 link	n.303-64C>T	intron_variant	Intron 3 of 3	5
IL1RN	ENST00000465812.6 link	n.647-2096C>T	intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23055

AN:

151950

Hom.:

2030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.0443

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

AF XY:

0.0735

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0714

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23053

AN:

152068

Hom.:

2030

Cov.:

AF XY:

0.147

AC XY:

10919

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0927

AC:

3846

AN:

41482

American (AMR)

AF:

0.116

AC:

1768

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

650

AN:

3470

East Asian (EAS)

AF:

0.0221

AC:

114

AN:

5168

South Asian (SAS)

AF:

0.0439

AC:

212

AN:

4824

European-Finnish (FIN)

AF:

0.157

AC:

1655

AN:

10574

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14346

AN:

67964

Other (OTH)

AF:

0.140

AC:

295

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

956

1912

2869

3825

4781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.184

Hom.:

5140

Bravo

AF:

0.146

Asia WGS

AF:

0.0290

AC:

105

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.79

(source)

DANN

Benign

0.69

PhyloP100

-2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over