NM_005535.3:c.1989A>G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_005535.3(IL12RB1):āc.1989A>Gā(p.Ter663Trpext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000723 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005535.3 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL12RB1 | ENST00000593993.7 | c.1989A>G | p.Ter663Trpext*? | stop_lost | Exon 17 of 17 | 1 | NM_005535.3 | ENSP00000472165.2 | ||
IL12RB1 | ENST00000600835.6 | c.1989A>G | p.Ter663Trpext*? | stop_lost | Exon 18 of 18 | 1 | ENSP00000470788.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246154Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133778
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 628336Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 342266
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74326
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency Uncertain:1
This sequence change disrupts the translational stop signal of the IL12RB1 mRNA. It is expected to extend the length of the IL12RB1 protein by 9 additional amino acid residues. This variant is present in population databases (rs372358188, gnomAD 0.02%). 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: 1981311). 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