dbSNP rs383483: IL12RB1:c.1791+46T>C (chr19-18061076-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246

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=-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 rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3 link	c.1791+46T>C		intron_variant	Intron 15 of 16	ENST00000593993.7	NP_005526.1	P42701-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7 link	c.1791+46T>C		intron_variant	Intron 15 of 16	1	NM_005535.3	ENSP00000472165.2		P42701-1
IL12RB1	ENST00000600835.6 link	c.1791+46T>C		intron_variant	Intron 16 of 17	1		ENSP00000470788.1		P42701-1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74540

AN:

151888

Hom.:

18621

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.478

AC XY:

203847

AN XY:

426374

show subpopulations

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.:

AF XY:

0.489

AC XY:

36339

AN XY:

74274

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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