dbSNP rs919766: IL12B:c.483-36T>G (chr5-159320556-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002187.3(IL12B):c.483-36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,547,022 control chromosomes in the GnomAD database, including 11,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1811 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9562 hom. )

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.248

Variant links:

Genes affected

IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

IL12B links:

ENSG00000249738 (HGNC:58156):

ENSG00000249738 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 5-159320556-A-C is Benign according to our data. Variant chr5-159320556-A-C is described in ClinVar as [Benign]. Clinvar id is 2628262.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3 link	c.483-36T>G		intron_variant	Intron 4 of 7	ENST00000231228.3	NP_002178.2	P29460

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL12B	ENST00000231228.3 link	c.483-36T>G	intron_variant	Intron 4 of 7	1	NM_002187.3	ENSP00000231228.2	P29460
IL12B	ENST00000696750.1 link	c.-148-36T>G	intron_variant	Intron 1 of 4			ENSP00000512849.1	A0A8Q3WML5
ENSG00000249738	ENST00000521472.6 link	n.290-4978A>C	intron_variant	Intron 2 of 3	3
IL12B	ENST00000696751.1 link	n.365-36T>G	intron_variant	Intron 3 of 6			ENSP00000512850.1	A0A8Q3SJ12

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21409

AN:

152126

Hom.:

1796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0395

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.0711

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.119

AC:

29470

AN:

247156

Hom.:

2135

AF XY:

0.114

AC XY:

15202

AN XY:

133880

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.0712

Gnomad FIN exome

AF:

0.0726

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.111

AC:

155515

AN:

1394778

Hom.:

9562

Cov.:

AF XY:

0.110

AC XY:

76610

AN XY:

697870

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.0415

Gnomad4 SAS exome

AF:

0.0715

Gnomad4 FIN exome

AF:

0.0719

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.141

AC:

21455

AN:

152244

Hom.:

1811

Cov.:

AF XY:

0.136

AC XY:

10140

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.0396

Gnomad4 SAS

AF:

0.0650

Gnomad4 FIN

AF:

0.0711

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.131

Hom.:

492

Bravo

AF:

0.153

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

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 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.53

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