rs79972275
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005535.3(IL12RB1):c.783+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00913 in 1,573,350 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0056 ( 7 hom., cov: 31)
Exomes 𝑓: 0.0095 ( 107 hom. )
Consequence
IL12RB1
NM_005535.3 intron
NM_005535.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.526
Genes affected
IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
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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=-0.9).
BP6
?
Variant 19-18073507-G-A is Benign according to our data. Variant chr19-18073507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 328591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18073507-G-A is described in Lovd as [Likely_benign]. Variant chr19-18073507-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00564 (858/152024) while in subpopulation SAS AF= 0.0106 (51/4810). AF 95% confidence interval is 0.00871. There are 7 homozygotes in gnomad4. There are 378 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL12RB1 | NM_005535.3 | c.783+10C>T | intron_variant | ENST00000593993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL12RB1 | ENST00000593993.7 | c.783+10C>T | intron_variant | 1 | NM_005535.3 | P1 | |||
IL12RB1 | ENST00000322153.11 | c.783+10C>T | intron_variant | 1 | |||||
IL12RB1 | ENST00000600835.6 | c.783+10C>T | intron_variant | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00565 AC: 859AN: 151906Hom.: 7 Cov.: 31
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GnomAD3 exomes AF: 0.00648 AC: 1624AN: 250570Hom.: 11 AF XY: 0.00695 AC XY: 942AN XY: 135576
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GnomAD4 exome AF: 0.00950 AC: 13507AN: 1421326Hom.: 107 Cov.: 28 AF XY: 0.00966 AC XY: 6850AN XY: 709278
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GnomAD4 genome ? AF: 0.00564 AC: 858AN: 152024Hom.: 7 Cov.: 31 AF XY: 0.00509 AC XY: 378AN XY: 74310
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Immunodeficiency 27A Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Dec 09, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 28, 2017 | - - |
IL12RB1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 26, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at