Genetic Variant IL12B:c.364+49A>G (chr5-159323005-T-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.364+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,571,908 control chromosomes in the GnomAD database, including 46,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5925 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40321 hom. )

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.676

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=-0.87).

BP6

Variant 5-159323005-T-C is Benign according to our data. Variant chr5-159323005-T-C is described in ClinVar as [Benign]. Clinvar id is 2628167.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3 link	c.364+49A>G		intron_variant	Intron 3 of 7	ENST00000231228.3	NP_002178.2	P29460

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL12B	ENST00000231228.3 link	c.364+49A>G	intron_variant	Intron 3 of 7	1	NM_002187.3	ENSP00000231228.2	P29460
IL12B	ENST00000696750.1 link	c.-148-2485A>G	intron_variant	Intron 1 of 4			ENSP00000512849.1	A0A8Q3WML5
ENSG00000249738	ENST00000521472.6 link	n.290-2529T>C	intron_variant	Intron 2 of 3	3
IL12B	ENST00000696751.1 link	n.364+49A>G	intron_variant	Intron 3 of 6			ENSP00000512850.1	A0A8Q3SJ12

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40313

AN:

151944

Hom.:

5919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.276

AC:

67883

AN:

245918

Hom.:

10653

AF XY:

0.273

AC XY:

36468

AN XY:

133690

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.390

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.466

Gnomad SAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.225

AC:

319858

AN:

1419846

Hom.:

40321

Cov.:

AF XY:

0.228

AC XY:

161638

AN XY:

708682

show subpopulations

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.265

AC:

40343

AN:

152062

Hom.:

5925

Cov.:

AF XY:

0.269

AC XY:

20019

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.475

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.287

Alfa

AF:

0.225

Hom.:

4250

Bravo

AF:

0.282

Asia WGS

AF:

0.438

AC:

1518

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 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 51. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.63

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