rs11086087

Positions:

Variant summary

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

The ENST00000593993.7(IL12RB1):c.387G>C(p.Val129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,610,028 control chromosomes in the GnomAD database, including 10,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 940 hom., cov: 30)

Exomes 𝑓: 0.11 ( 9598 hom. )

Consequence

IL12RB1
ENST00000593993.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.575

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 19-18080854-C-G is Benign according to our data. Variant chr19-18080854-C-G is described in ClinVar as [Benign]. Clinvar id is 328599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.575 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12RB1	NM_005535.3 linkuse as main transcript	c.387G>C	p.Val129=	synonymous_variant	4/17	ENST00000593993.7	NP_005526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12RB1	ENST00000593993.7 linkuse as main transcript	c.387G>C	p.Val129=	synonymous_variant	4/17	1	NM_005535.3	ENSP00000472165	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.387G>C	p.Val129=	synonymous_variant	5/18	1		ENSP00000470788	P1	P42701-1
IL12RB1	ENST00000322153.11 linkuse as main transcript	c.387G>C	p.Val129=	synonymous_variant	4/10	1		ENSP00000314425		P42701-3
IL12RB1	ENST00000430026.7 linkuse as main transcript			downstream_gene_variant		4		ENSP00000403103

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15394

AN:

152024

Hom.:

938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0941

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.119

AC:

29807

AN:

251420

Hom.:

2126

AF XY:

0.121

AC XY:

16462

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0534

Gnomad AMR exome

AF:

0.0740

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.111

AC:

161735

AN:

1457886

Hom.:

9598

Cov.:

AF XY:

0.112

AC XY:

81006

AN XY:

725538

show subpopulations

Gnomad4 AFR exome

AF:

0.0508

Gnomad4 AMR exome

AF:

0.0767

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.101

AC:

15410

AN:

152142

Hom.:

940

Cov.:

AF XY:

0.103

AC XY:

7633

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0552

Gnomad4 AMR

AF:

0.0939

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.113

Hom.:

332

Bravo

AF:

0.0985

Asia WGS

AF:

0.209

AC:

725

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.13

DANN

Benign

0.48

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