chr19-18059574-G-A

Position:

chr19-18059574-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005535.3(IL12RB1):c.*34C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 778,530 control chromosomes in the GnomAD database, including 45,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7318 hom., cov: 32)

Exomes 𝑓: 0.34 ( 38563 hom. )

Consequence

IL12RB1
NM_005535.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00200

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-18059574-G-A is Benign according to our data. Variant chr19-18059574-G-A is described in ClinVar as [Benign]. Clinvar id is 328572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 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.*34C>T		3_prime_UTR_variant	17/17	ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7 linkuse as main transcript	c.*34C>T		3_prime_UTR_variant	17/17	1	NM_005535.3	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.*34C>T		3_prime_UTR_variant	18/18	1		P1	P42701-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42868

AN:

151944

Hom.:

7318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.302

AC:

73419

AN:

243418

Hom.:

12488

AF XY:

0.308

AC XY:

40706

AN XY:

132174

show subpopulations

Gnomad AFR exome

AF:

0.0983

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.338

AC:

211489

AN:

626468

Hom.:

38563

Cov.:

AF XY:

0.336

AC XY:

114603

AN XY:

341138

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.387

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.282

AC:

42867

AN:

152062

Hom.:

7318

Cov.:

AF XY:

0.284

AC XY:

21085

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.387

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.319

Hom.:

1912

Bravo

AF:

0.255

Asia WGS

AF:

0.169

AC:

593

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.3

DANN

Benign

0.59

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