rs61734350

Positions:

chr19-18069637-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005535.3(IL12RB1):c.1098G>A(p.Thr366=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,613,436 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 13 hom. )

Consequence

IL12RB1
NM_005535.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.46

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=-0.84).

BP6

Variant 19-18069637-C-T is Benign according to our data. Variant chr19-18069637-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-18069637-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.46 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00242 (369/152322) while in subpopulation NFE AF= 0.00375 (255/68028). AF 95% confidence interval is 0.00337. There are 0 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12RB1	NM_005535.3 linkuse as main transcript	c.1098G>A	p.Thr366=	synonymous_variant	10/17	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.1098G>A	p.Thr366=	synonymous_variant	10/17	1	NM_005535.3	ENSP00000472165	P1	P42701-1
IL12RB1	ENST00000600835.6 linkuse as main transcript	c.1098G>A	p.Thr366=	synonymous_variant	11/18	1		ENSP00000470788	P1	P42701-1

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00290

AC:

721

AN:

248900

Hom.:

AF XY:

0.00307

AC XY:

415

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.00566

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.000377

Gnomad NFE exome

AF:

0.00380

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00298

AC:

4354

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

2262

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00308

Gnomad4 FIN exome

AF:

0.000490

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00242

AC:

369

AN:

152322

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.00255

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00516

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	IL12RB1: BP4, BP7 -

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.086

DANN

Benign

0.57

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