rs383483

chr19-18061076-A-G

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.1791+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 968,378 control chromosomes in the GnomAD database, including 116,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18647 hom., cov: 31)
  • Exomes 𝑓: 0.48 (97493 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246

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=-1.01).
• BP6: Variant 19-18061076-A-G is Benign according to our data. Variant chr19-18061076-A-G is described in ClinVar as [Benign]. Clinvar id is 2688394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_005535.3	c.1791+46T>C		intron_variant		ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7	c.1791+46T>C		intron_variant		1	NM_005535.3	P1
IL12RB1	ENST00000600835.6	c.1791+46T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74540 AN: 151888 Hom.: 18621 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.452 AC: 83826 AN: 185586 Hom.: 19728 AF XY: 0.452 AC XY: 44704 AN XY: 98882

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.373

Gnomad SAS exome AF: 0.326

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.483 AC: 394020 AN: 816372 Hom.: 97493 Cov.: 11 AF XY: 0.478 AC XY: 203847 AN XY: 426374

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.491 AC: 74594 AN: 152006 Hom.: 18647 Cov.: 31 AF XY: 0.489 AC XY: 36339 AN XY: 74274

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.475

Alfa AF: 0.503 Hom.: 3486

Bravo AF: 0.477

Asia WGS AF: 0.402 AC: 1399 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 59% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.1
Dann	Benign	0.64

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: rs383483; hg19: chr19-18171886; COSMIC: COSV74045534;