rs17852635

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005535.3(IL12RB1):c.684C>T(p.Pro228Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,610,226 control chromosomes in the GnomAD database, including 75,834 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. P228P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.25 ( 5580 hom., cov: 31)

Exomes 𝑓: 0.31 ( 70254 hom. )

Consequence

IL12RB1
NM_005535.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.47

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

IL12RB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-18075765-G-A is Benign according to our data. Variant chr19-18075765-G-A is described in ClinVar as Benign. ClinVar VariationId is 328596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12RB1	NM_005535.3 link	c.684C>T	p.Pro228Pro	synonymous_variant	Exon 7 of 17	ENST00000593993.7	NP_005526.1	P42701-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL12RB1	ENST00000593993.7 link	c.684C>T	p.Pro228Pro	synonymous_variant	Exon 7 of 17	1	NM_005535.3	ENSP00000472165.2	P42701-1
IL12RB1	ENST00000600835.6 link	c.684C>T	p.Pro228Pro	synonymous_variant	Exon 8 of 18	1		ENSP00000470788.1	P42701-1
IL12RB1	ENST00000322153.11 link	c.684C>T	p.Pro228Pro	synonymous_variant	Exon 7 of 10	1		ENSP00000314425.5	P42701-3

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38678

AN:

151868

Hom.:

5570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.277

AC:

69678

AN:

251328

AF XY:

0.283

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.306

AC:

445884

AN:

1458240

Hom.:

70254

Cov.:

AF XY:

0.305

AC XY:

221407

AN XY:

725652

show subpopulations

African (AFR)

AF:

0.120

AC:

4022

AN:

33440

American (AMR)

AF:

0.167

AC:

7459

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8696

AN:

26112

East Asian (EAS)

AF:

0.385

AC:

15271

AN:

39658

South Asian (SAS)

AF:

0.231

AC:

19873

AN:

86202

European-Finnish (FIN)

AF:

0.325

AC:

17348

AN:

53368

Middle Eastern (MID)

AF:

0.299

AC:

1725

AN:

5766

European-Non Finnish (NFE)

AF:

0.319

AC:

353458

AN:

1108700

Other (OTH)

AF:

0.299

AC:

18032

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

15104

30208

45313

60417

75521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11376

22752

34128

45504

56880

<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:

0.255

AC:

38713

AN:

151986

Hom.:

5580

Cov.:

AF XY:

0.256

AC XY:

19047

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.126

AC:

5211

AN:

41474

American (AMR)

AF:

0.206

AC:

3147

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1128

AN:

3470

East Asian (EAS)

AF:

0.371

AC:

1917

AN:

5168

South Asian (SAS)

AF:

0.239

AC:

1152

AN:

4820

European-Finnish (FIN)

AF:

0.337

AC:

3555

AN:

10548

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21747

AN:

67958

Other (OTH)

AF:

0.266

AC:

558

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1431

2861

4292

5722

7153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.289

Hom.:

10675

Bravo

AF:

0.239

Asia WGS

AF:

0.322

AC:

1120

AN:

3478

EpiCase

AF:

0.321

EpiControl

AF:

0.316

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 31. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.12

(source)

DANN

Benign

0.59

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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