dbSNP rs315950: IL1RN:c.*1357G>A (chr2-113134228-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.*1357G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,286 control chromosomes in the GnomAD database, including 69,660 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 0.95 ( 69660 hom., cov: 33)

Consequence

IL1RN
NM_173841.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.386

Publications

4 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 = 0.993 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	Tags	HGVSc	Effect	Exon Rank	Protein
IL1RN	NM_173842.3	MANE Select	c.*1357G>A	downstream_gene	N/A	NP_776214.1
IL1RN	NM_173841.3		c.*1357G>A	downstream_gene	N/A	NP_776213.1
IL1RN	NM_000577.5		c.*1357G>A	downstream_gene	N/A	NP_000568.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL1RN	ENST00000409930.4	TSL:1 MANE Select	c.*1357G>A	downstream_gene	N/A	ENSP00000387173.3
IL1RN	ENST00000259206.9	TSL:1	c.*1357G>A	downstream_gene	N/A	ENSP00000259206.5
IL1RN	ENST00000354115.6	TSL:1	c.*1357G>A	downstream_gene	N/A	ENSP00000329072.3

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145167

AN:

152168

Hom.:

69620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.979

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.968

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

GnomAD4 genome

AF:

0.954

AC:

145262

AN:

152286

Hom.:

69660

Cov.:

AF XY:

0.955

AC XY:

71156

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.841

AC:

34927

AN:

41506

American (AMR)

AF:

0.979

AC:

14981

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

3461

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5186

AN:

5186

South Asian (SAS)

AF:

0.999

AC:

4829

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10628

AN:

10628

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

68000

AN:

68042

Other (OTH)

AF:

0.968

AC:

2045

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

292

585

877

1170

1462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.968

Hom.:

9236

Bravo

AF:

0.947

Asia WGS

AF:

0.990

AC:

3443

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.42

(source)

DANN

Benign

0.61

PhyloP100

-0.39

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