rs776936363
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005535.3(IL12RB1):āc.1621G>Cā(p.Val541Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,605,464 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V541M) has been classified as Uncertain significance.
Frequency
Consequence
NM_005535.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL12RB1 | NM_005535.3 | c.1621G>C | p.Val541Leu | missense_variant, splice_region_variant | 14/17 | ENST00000593993.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL12RB1 | ENST00000593993.7 | c.1621G>C | p.Val541Leu | missense_variant, splice_region_variant | 14/17 | 1 | NM_005535.3 | P1 | |
IL12RB1 | ENST00000600835.6 | c.1621G>C | p.Val541Leu | missense_variant, splice_region_variant | 15/18 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246974Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134044
GnomAD4 exome AF: 0.0000337 AC: 49AN: 1453316Hom.: 0 Cov.: 28 AF XY: 0.0000249 AC XY: 18AN XY: 723238
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 541 of the IL12RB1 protein (p.Val541Leu). This variant is present in population databases (rs776936363, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with IL12RB1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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