Variant 19-18059847-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005535.3(IL12RB1):c.1983+47G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,050,200 control chromosomes in the GnomAD database, including 78,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7505 hom., cov: 31)

Exomes 𝑓: 0.36 ( 71445 hom. )

Consequence

IL12RB1
NM_005535.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-18059847-C-A is Benign according to our data. Variant chr19-18059847-C-A is described in ClinVar as [Benign]. Clinvar id is 2688418.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_005535.3 linkuse as main transcript	c.1983+47G>T		intron_variant		ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7 linkuse as main transcript	c.1983+47G>T		intron_variant		1	NM_005535.3	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.1983+47G>T		intron_variant		1		P1	P42701-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42171

AN:

151902

Hom.:

7505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.305

AC:

48467

AN:

158674

Hom.:

8477

AF XY:

0.310

AC XY:

26022

AN XY:

84012

show subpopulations

Gnomad AFR exome

AF:

0.0616

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.359

AC:

322080

AN:

898180

Hom.:

71445

Cov.:

AF XY:

0.356

AC XY:

164783

AN XY:

462414

show subpopulations

Gnomad4 AFR exome

AF:

0.0566

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.277

AC:

42164

AN:

152020

Hom.:

7505

Cov.:

AF XY:

0.279

AC XY:

20709

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.277

Hom.:

1351

Bravo

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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 49% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over