rs2307153

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374259.2(IL12RB2):c.1394G>A(p.Gly465Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,610,054 control chromosomes in the GnomAD database, including 342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 21 hom., cov: 32)

Exomes 𝑓: 0.019 ( 321 hom. )

Consequence

IL12RB2
NM_001374259.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.840

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003908336).

BP6

Variant 1-67367960-G-A is Benign according to our data. Variant chr1-67367960-G-A is described in ClinVar as Benign. ClinVar VariationId is 1166571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0146 (2229/152266) while in subpopulation NFE AF = 0.0226 (1539/68010). AF 95% confidence interval is 0.0217. There are 21 homozygotes in GnomAd4. There are 1067 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB2	NM_001374259.2 link	c.1394G>A	p.Gly465Asp	missense_variant	Exon 11 of 17	ENST00000674203.2	NP_001361188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12RB2	ENST00000674203.2 link	c.1394G>A	p.Gly465Asp	missense_variant	Exon 11 of 17		NM_001374259.2	ENSP00000501329.1		Q99665-1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2229

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0226

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.0139

AC:

3498

AN:

251434

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.00971

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0220

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0195

AC:

28393

AN:

1457788

Hom.:

321

Cov.:

AF XY:

0.0190

AC XY:

13804

AN XY:

725540

show subpopulations

African (AFR)

AF:

0.00353

AC:

118

AN:

33416

American (AMR)

AF:

0.0108

AC:

484

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00234

AC:

AN:

26110

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39680

South Asian (SAS)

AF:

0.000592

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.0222

AC:

1187

AN:

53418

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0229

AC:

25410

AN:

1108278

Other (OTH)

AF:

0.0178

AC:

1070

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0146

AC:

2229

AN:

152266

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1067

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00407

AC:

169

AN:

41558

American (AMR)

AF:

0.0159

AC:

243

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0225

AC:

239

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0226

AC:

1539

AN:

68010

Other (OTH)

AF:

0.0128

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

216

323

431

539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0191

Hom.:

125

Bravo

AF:

0.0137

TwinsUK

AF:

0.0256

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0190

AC:

163

ExAC

AF:

0.0141

AC:

1711

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0206

EpiControl

AF:

0.0198

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

IL12RB2-related disorder

Benign:1

Mar 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.14

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.069

T;.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.52

.;T;T;T;T

MetaRNN

Benign

0.0039

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.9

M;M;.;M;M

PhyloP100

-0.84

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.5

N;N;N;N;.

REVEL

Benign

0.038

Sift

Benign

0.13

T;T;T;T;.

Sift4G

Uncertain

0.0070

D;D;D;D;.

Polyphen

0.0020

B;.;.;B;B

Vest4

0.018

MPC

0.18

ClinPred

0.012

GERP RS

-3.2

Varity_R

0.096

gMVP

0.48

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over