rs4297265

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001374259.2(IL12RB2):c.1929G>A(p.Thr643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,607,342 control chromosomes in the GnomAD database, including 259,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18804 hom., cov: 29)

Exomes 𝑓: 0.57 ( 240265 hom. )

Consequence

IL12RB2
NM_001374259.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.599

Variant links:

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

IL12RB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-67386652-G-A is Benign according to our data. Variant chr1-67386652-G-A is described in ClinVar as [Benign]. Clinvar id is 1170882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.599 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB2	NM_001374259.2 linkuse as main transcript	c.1929G>A	p.Thr643=	synonymous_variant	15/17	ENST00000674203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB2	ENST00000674203.2 linkuse as main transcript	c.1929G>A	p.Thr643=	synonymous_variant	15/17		NM_001374259.2	P1	Q99665-1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71023

AN:

151432

Hom.:

18801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.528

AC:

132759

AN:

251390

Hom.:

36875

AF XY:

0.539

AC XY:

73241

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.692

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.568

AC:

827042

AN:

1455794

Hom.:

240265

Cov.:

AF XY:

0.569

AC XY:

412601

AN XY:

724690

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.452

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.535

GnomAD4 genome

AF:

0.469

AC:

71031

AN:

151548

Hom.:

18804

Cov.:

AF XY:

0.475

AC XY:

35156

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.545

Hom.:

40457

Bravo

AF:

0.435

Asia WGS

AF:

0.390

AC:

1358

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

Cadd

Benign

1.1

Dann

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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