chr5-159314825-AAAAT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_002187.3(IL12B):c.*1272_*1275del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 152,362 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
IL12B
NM_002187.3 3_prime_UTR
NM_002187.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.780
Genes affected
IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00255 (388/152362) while in subpopulation AFR AF= 0.0089 (370/41584). AF 95% confidence interval is 0.00815. There are 1 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL12B | NM_002187.3 | c.*1272_*1275del | 3_prime_UTR_variant | 8/8 | ENST00000231228.3 | ||
LOC105377683 | XR_941138.3 | n.401-377_401-374del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL12B | ENST00000231228.3 | c.*1272_*1275del | 3_prime_UTR_variant | 8/8 | 1 | NM_002187.3 | P1 | ||
IL12B | ENST00000696750.1 | c.*1272_*1275del | 3_prime_UTR_variant | 5/5 | |||||
IL12B | ENST00000696751.1 | c.*1754_*1757del | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | |||||
ENST00000521472.6 | n.289+3427_289+3430del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00255 AC: 388AN: 152244Hom.: 1 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 132Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 74
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GnomAD4 genome AF: 0.00255 AC: 388AN: 152362Hom.: 1 Cov.: 32 AF XY: 0.00234 AC XY: 174AN XY: 74518
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial Atypical Mycobacteriosis, Autosomal Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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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