Variant rs2229546 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001374259.2(IL12RB2):c.2337C>A(p.Pro779=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,609,934 control chromosomes in the GnomAD database, including 352,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P779P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.61 ( 29460 hom., cov: 32)

Exomes 𝑓: 0.66 ( 322814 hom. )

Consequence

IL12RB2
NM_001374259.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.86

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-67395837-C-A is Benign according to our data. Variant chr1-67395837-C-A is described in ClinVar as [Benign]. Clinvar id is 1164694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 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.2337C>A	p.Pro779=	synonymous_variant	17/17	ENST00000674203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB2	ENST00000674203.2 linkuse as main transcript	c.2337C>A	p.Pro779=	synonymous_variant	17/17		NM_001374259.2	P1	Q99665-1

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93381

AN:

151976

Hom.:

29456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.594

GnomAD3 exomes

AF:

0.629

AC:

157582

AN:

250566

Hom.:

50702

AF XY:

0.637

AC XY:

86203

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.570

Gnomad ASJ exome

AF:

0.668

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.662

AC:

964858

AN:

1457840

Hom.:

322814

Cov.:

AF XY:

0.663

AC XY:

480592

AN XY:

724676

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.566

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.741

Gnomad4 NFE exome

AF:

0.678

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.614

AC:

93423

AN:

152094

Hom.:

29460

Cov.:

AF XY:

0.617

AC XY:

45861

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.588

Gnomad4 ASJ

AF:

0.670

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.676

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.645

Hom.:

35215

Bravo

AF:

0.592

Asia WGS

AF:

0.488

AC:

1697

AN:

3478

EpiCase

AF:

0.673

EpiControl

AF:

0.666

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 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. 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

-0.77

CADD

Benign

0.053

DANN

Benign

0.36

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