chr5-159323171-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002187.3(IL12B):c.247G>A(p.Gly83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002187.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL12B | NM_002187.3 | c.247G>A | p.Gly83Arg | missense_variant | 3/8 | ENST00000231228.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL12B | ENST00000231228.3 | c.247G>A | p.Gly83Arg | missense_variant | 3/8 | 1 | NM_002187.3 | P1 | |
IL12B | ENST00000696750.1 | c.-148-2651G>A | intron_variant | ||||||
IL12B | ENST00000696751.1 | c.247G>A | p.Gly83Arg | missense_variant, NMD_transcript_variant | 3/7 | ||||
ENST00000521472.6 | n.290-2363C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135852
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461848Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727224
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2017 | This sequence change replaces glycine with arginine at codon 83 of the IL12B protein (p.Gly83Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs756537897, ExAC 0.001%). This variant has not been reported in the literature in individuals with IL12B-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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