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rs419598

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173842.3(IL1RN):c.171T>C(p.Ala57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,609,674 control chromosomes in the GnomAD database, including 59,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4288 hom., cov: 32)
Exomes 𝑓: 0.27 ( 55095 hom. )

Consequence

IL1RN
NM_173842.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.00
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 2-113129630-T-C is Benign according to our data. Variant chr2-113129630-T-C is described in ClinVar as [Benign]. Clinvar id is 330825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113129630-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL1RNNM_173842.3 linkuse as main transcriptc.171T>C p.Ala57= synonymous_variant 2/4 ENST00000409930.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1RNENST00000409930.4 linkuse as main transcriptc.171T>C p.Ala57= synonymous_variant 2/41 NM_173842.3 P4P18510-1

Frequencies

GnomAD3 genomes
AF:
0.216
AC:
32829
AN:
152038
Hom.:
4280
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0704
Gnomad AMI
AF:
0.248
Gnomad AMR
AF:
0.282
Gnomad ASJ
AF:
0.291
Gnomad EAS
AF:
0.0777
Gnomad SAS
AF:
0.288
Gnomad FIN
AF:
0.305
Gnomad MID
AF:
0.215
Gnomad NFE
AF:
0.276
Gnomad OTH
AF:
0.239
GnomAD3 exomes
AF:
0.256
AC:
64470
AN:
251432
Hom.:
9252
AF XY:
0.259
AC XY:
35246
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0651
Gnomad AMR exome
AF:
0.321
Gnomad ASJ exome
AF:
0.297
Gnomad EAS exome
AF:
0.0708
Gnomad SAS exome
AF:
0.285
Gnomad FIN exome
AF:
0.305
Gnomad NFE exome
AF:
0.273
Gnomad OTH exome
AF:
0.266
GnomAD4 exome
AF:
0.268
AC:
390790
AN:
1457516
Hom.:
55095
Cov.:
30
AF XY:
0.268
AC XY:
194275
AN XY:
725298
show subpopulations
Gnomad4 AFR exome
AF:
0.0625
Gnomad4 AMR exome
AF:
0.317
Gnomad4 ASJ exome
AF:
0.289
Gnomad4 EAS exome
AF:
0.0600
Gnomad4 SAS exome
AF:
0.281
Gnomad4 FIN exome
AF:
0.300
Gnomad4 NFE exome
AF:
0.278
Gnomad4 OTH exome
AF:
0.256
GnomAD4 genome
AF:
0.216
AC:
32867
AN:
152158
Hom.:
4288
Cov.:
32
AF XY:
0.219
AC XY:
16273
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0708
Gnomad4 AMR
AF:
0.283
Gnomad4 ASJ
AF:
0.291
Gnomad4 EAS
AF:
0.0771
Gnomad4 SAS
AF:
0.289
Gnomad4 FIN
AF:
0.305
Gnomad4 NFE
AF:
0.276
Gnomad4 OTH
AF:
0.240
Alfa
AF:
0.264
Hom.:
9069
Bravo
AF:
0.206
Asia WGS
AF:
0.196
AC:
683
AN:
3478
EpiCase
AF:
0.272
EpiControl
AF:
0.268

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant associated with alopecia, ankylosing spondylitis, hypertension in pregnancy, carotid atherosclerosis - dubious and not relevant to patient disease -
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -
Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021This variant is associated with the following publications: (PMID: 17899305, 8641687, 19818512, 12624309, 11841485) -
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenJan 14, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
2.3
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs419598; hg19: chr2-113887207; COSMIC: COSV52080055; API