Variant 19-18059870-G-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+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,329,962 control chromosomes in the GnomAD database, including 101,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7534 hom., cov: 31)

Exomes 𝑓: 0.40 ( 94286 hom. )

Consequence

IL12RB1
NM_005535.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

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=-0.9).

BP6

Variant 19-18059870-G-A is Benign according to our data. Variant chr19-18059870-G-A is described in ClinVar as [Benign]. Clinvar id is 2688417.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 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+24C>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+24C>T		intron_variant		1	NM_005535.3	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.1983+24C>T		intron_variant		1		P1	P42701-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

42403

AN:

149568

Hom.:

7533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0766

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.308

AC:

52467

AN:

170374

Hom.:

9195

AF XY:

0.313

AC XY:

28353

AN XY:

90660

show subpopulations

Gnomad AFR exome

AF:

0.0682

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.462

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.401

AC:

473059

AN:

1180292

Hom.:

94286

Cov.:

AF XY:

0.396

AC XY:

234546

AN XY:

592346

show subpopulations

Gnomad4 AFR exome

AF:

0.0748

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.283

AC:

42401

AN:

149670

Hom.:

7534

Cov.:

AF XY:

0.285

AC XY:

20831

AN XY:

73036

show subpopulations

Gnomad4 AFR

AF:

0.0766

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.339

Hom.:

1955

Bravo

AF:

0.252

Asia WGS

AF:

0.170

AC:

595

AN:

3478

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 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.085

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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