19-18090456-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600835.6(IL12RB1):c.-109-3524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,132 control chromosomes in the GnomAD database, including 44,609 homozygotes. 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: 𝑓 0.76 (44609 hom., cov: 32)
• Consequence: IL12RB1 ENST00000600835.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_001290024.1	c.12-3524G>A		intron_variant
IL12RB1	XM_006722741.4	c.12-3524G>A		intron_variant
IL12RB1	XM_011527966.3	c.12-3524G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000600835.6	c.-109-3524G>A		intron_variant		1		P1
IL12RB1	ENST00000594176.1	c.-110+194G>A		intron_variant		4
IL12RB1	ENST00000598019.6	c.-110+194G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116090 AN: 152014 Hom.: 44561 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.745

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.764 AC: 116194 AN: 152132 Hom.: 44609 Cov.: 32 AF XY: 0.768 AC XY: 57101 AN XY: 74376

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.749

Alfa AF: 0.736 Hom.: 41588

Bravo AF: 0.753

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374326; hg19: chr19-18201266;