chr19-18090456-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000600835.6(IL12RB1):​c.-109-3524G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

IL12RB1
ENST00000600835.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0180

Publications

12 publications found
Variant links:
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]
IL12RB1 Gene-Disease associations (from GenCC):
  • Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL12RB1NM_001290024.2 linkc.12-3524G>T intron_variant Intron 1 of 17 NP_001276953.1
IL12RB1NM_001440426.1 linkc.12-3524G>T intron_variant Intron 1 of 10 NP_001427355.1
IL12RB1NM_001440427.1 linkc.12-3524G>T intron_variant Intron 1 of 10 NP_001427356.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL12RB1ENST00000600835.6 linkc.-109-3524G>T intron_variant Intron 1 of 17 1 ENSP00000470788.1 P42701-1
IL12RB1ENST00000598019.6 linkc.-110+194G>T intron_variant Intron 3 of 5 4 ENSP00000468831.2 M0QX06
IL12RB1ENST00000594176.1 linkc.-110+194G>T intron_variant Intron 2 of 4 4 ENSP00000473051.1 M0R382

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.1
DANN
Benign
0.42
PhyloP100
0.018

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs374326; hg19: chr19-18201266; API