19-18069654-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005535.3(IL12RB1):āc.1081C>Gā(p.Arg361Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005535.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL12RB1 | ENST00000593993.7 | c.1081C>G | p.Arg361Gly | missense_variant | Exon 10 of 17 | 1 | NM_005535.3 | ENSP00000472165.2 | ||
IL12RB1 | ENST00000600835.6 | c.1081C>G | p.Arg361Gly | missense_variant | Exon 11 of 18 | 1 | ENSP00000470788.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248962Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135102
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460784Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726752
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74480
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 361 of the IL12RB1 protein (p.Arg361Gly). This variant is present in population databases (rs150261140, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with IL12RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 965371). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt IL12RB1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at