Variant 5-159316838-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002187.3(IL12B):c.856-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,612,714 control chromosomes in the GnomAD database, including 11,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1471 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9707 hom. )

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.292

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:):

ENSG00000249738 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-159316838-G-A is Benign according to our data. Variant chr5-159316838-G-A is described in ClinVar as [Benign]. Clinvar id is 2628273.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12B	NM_002187.3 linkuse as main transcript	c.856-22C>T		intron_variant		ENST00000231228.3	NP_002178.2	P29460

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IL12B	ENST00000231228.3 linkuse as main transcript	c.856-22C>T	intron_variant	1	NM_002187.3	ENSP00000231228.2	P29460
IL12B	ENST00000696750.1 linkuse as main transcript	c.226-22C>T	intron_variant			ENSP00000512849.1	A0A8Q3WML5
ENSG00000249738	ENST00000521472.6 linkuse as main transcript	n.289+5424G>A	intron_variant	3
IL12B	ENST00000696751.1 linkuse as main transcript	n.*351-22C>T	intron_variant			ENSP00000512850.1	A0A8Q3SJ12

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20124

AN:

152132

Hom.:

1464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.0647

Gnomad FIN

AF:

0.0709

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.116

AC:

28627

AN:

245750

Hom.:

2026

AF XY:

0.111

AC XY:

14835

AN XY:

133172

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.0458

Gnomad SAS exome

AF:

0.0708

Gnomad FIN exome

AF:

0.0729

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.110

AC:

161074

AN:

1460464

Hom.:

9707

Cov.:

AF XY:

0.109

AC XY:

78930

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.0417

Gnomad4 SAS exome

AF:

0.0715

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.132

AC:

20148

AN:

152250

Hom.:

1471

Cov.:

AF XY:

0.128

AC XY:

9519

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.0403

Gnomad4 SAS

AF:

0.0646

Gnomad4 FIN

AF:

0.0709

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.127

Hom.:

1465

Bravo

AF:

0.143

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.2

DANN

Benign

0.84

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

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