rs2234679
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000259206.9(IL1RN):c.-12G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,519,538 control chromosomes in the GnomAD database, including 50,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 4082 hom., cov: 33)
Exomes 𝑓: 0.25 ( 46386 hom. )
Consequence
IL1RN
ENST00000259206.9 5_prime_UTR
ENST00000259206.9 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.323
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 2-113118007-G-C is Benign according to our data. Variant chr2-113118007-G-C is described in ClinVar as [Benign]. Clinvar id is 330821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-113118007-G-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL1RN | NM_000577.5 | c.-12G>C | 5_prime_UTR_variant | 1/5 | |||
IL1RN | NM_001318914.2 | c.-294G>C | 5_prime_UTR_variant | 1/7 | |||
IL1RN | NM_173841.3 | c.-12G>C | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RN | ENST00000259206.9 | c.-12G>C | 5_prime_UTR_variant | 1/6 | 1 | ||||
IL1RN | ENST00000354115.6 | c.-12G>C | 5_prime_UTR_variant | 1/5 | 1 | A1 | |||
IL1RN | ENST00000361779.7 | c.-231G>C | 5_prime_UTR_variant | 1/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.209 AC: 31816AN: 152078Hom.: 4075 Cov.: 33
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GnomAD3 exomes AF: 0.253 AC: 63662AN: 251438Hom.: 9031 AF XY: 0.256 AC XY: 34804AN XY: 135902
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GnomAD4 exome AF: 0.253 AC: 345495AN: 1367340Hom.: 46386 Cov.: 22 AF XY: 0.254 AC XY: 173843AN XY: 685680
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GnomAD4 genome ? AF: 0.209 AC: 31833AN: 152198Hom.: 4082 Cov.: 33 AF XY: 0.212 AC XY: 15787AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 47. Only high quality variants are reported. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant 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: Frequency - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Sterile multifocal osteomyelitis with periostitis and pustulosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at