Variant 19-18060152-C-T 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.1792-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 840,986 control chromosomes in the GnomAD database, including 54,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 7478 hom., cov: 31)

Exomes 𝑓: 0.36 ( 46910 hom. )

Consequence

IL12RB1
NM_005535.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.28

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=-0.96).

BP6

Variant 19-18060152-C-T is Benign according to our data. Variant chr19-18060152-C-T is described in ClinVar as [Benign]. Clinvar id is 2688419.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 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.1792-67G>A		intron_variant		ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7 linkuse as main transcript	c.1792-67G>A		intron_variant		1	NM_005535.3	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.1792-67G>A		intron_variant		1		P1	P42701-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42453

AN:

151906

Hom.:

7477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.359

AC:

247378

AN:

688962

Hom.:

46910

AF XY:

0.356

AC XY:

128158

AN XY:

359634

show subpopulations

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.279

AC:

42451

AN:

152024

Hom.:

7478

Cov.:

AF XY:

0.281

AC XY:

20877

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.354

Hom.:

10495

Bravo

AF:

0.253

Asia WGS

AF:

0.169

AC:

593

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 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

-0.96

CADD

Benign

0.18

DANN

Benign

0.47

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

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