rs429774

chr19-18075942-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005535.3(IL12RB1):c.581-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,448,160 control chromosomes in the GnomAD database, including 68,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6126 hom., cov: 31)
  • Exomes 𝑓: 0.31 (62459 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-18075942-T-C is Benign according to our data. Variant chr19-18075942-T-C is described in ClinVar as [Benign]. Clinvar id is 2688447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_005535.3	c.581-74A>G		intron_variant		ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7	c.581-74A>G		intron_variant		1	NM_005535.3	P1
IL12RB1	ENST00000322153.11	c.581-74A>G		intron_variant		1
IL12RB1	ENST00000600835.6	c.581-74A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42047 AN: 151938 Hom.: 6111 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.306 AC: 396624 AN: 1296104 Hom.: 62459 AF XY: 0.305 AC XY: 199155 AN XY: 653078

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.277 AC: 42102 AN: 152056 Hom.: 6126 Cov.: 31 AF XY: 0.278 AC XY: 20637 AN XY: 74320

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.282

Alfa AF: 0.307 Hom.: 10277

Bravo AF: 0.264

Asia WGS AF: 0.326 AC: 1134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.3
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs429774; hg19: chr19-18186752; COSMIC: COSV59097392; COSMIC: COSV59097392;