rs182660189
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_005535.3(IL12RB1):c.1791+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000639 in 1,486,852 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
IL12RB1
NM_005535.3 intron
NM_005535.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0280
Genes affected
IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 19-18061113-C-T is Benign according to our data. Variant chr19-18061113-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 541823.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| IL12RB1 | NM_005535.3 | c.1791+9G>A | intron_variant | ENST00000593993.7 | NP_005526.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IL12RB1 | ENST00000593993.7 | c.1791+9G>A | intron_variant | 1 | NM_005535.3 | ENSP00000472165.2 | ||||
| IL12RB1 | ENST00000600835.6 | c.1791+9G>A | intron_variant | 1 | ENSP00000470788.1 |
Frequencies
GnomAD3 genomes 0.000237 AC: 36AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000480 AC: 11AN: 229396Hom.: 0 AF XY: 0.0000323 AC XY: 4AN XY: 123736
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GnomAD4 exome AF: 0.0000442 AC: 59AN: 1334528Hom.: 0 Cov.: 20 AF XY: 0.0000404 AC XY: 27AN XY: 668710
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GnomAD4 genome 0.000236 AC: 36AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74488
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 25, 2023 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Jan 18, 2023 | This variant has not been reported in the literature is present in the Genome Aggregation Database (Highest reported MAF 0.08% [13/15276]; https://gnomad.broadinstitute.org/variant/19-18061113-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID: 541823). Evolutionary conservation and computational prediction tools for this variant are limited or unavailable. This is an intronic variant with no predicted change in the amino acid sequence, but it may have an unknown effect on splicing. Splice prediction tools do not suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at