dbSNP rs2421047: IL12B:c.698-406C>T (chr5-159319299-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002187.3(IL12B):c.698-406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,120 control chromosomes in the GnomAD database, including 5,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5591 hom., cov: 33)

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

IL12B links:

ENSG00000249738 (HGNC:58156):

ENSG00000249738 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3 link	c.698-406C>T		intron_variant	Intron 5 of 7	ENST00000231228.3	NP_002178.2	P29460

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3 link	c.698-406C>T		intron_variant	Intron 5 of 7	1	NM_002187.3	ENSP00000231228.2		P29460

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39325

AN:

152002

Hom.:

5585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.259

AC:

39354

AN:

152120

Hom.:

5591

Cov.:

AF XY:

0.263

AC XY:

19539

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.318

AC:

13192

AN:

41496

American (AMR)

AF:

0.332

AC:

5067

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3466

East Asian (EAS)

AF:

0.465

AC:

2405

AN:

5174

South Asian (SAS)

AF:

0.363

AC:

1752

AN:

4828

European-Finnish (FIN)

AF:

0.179

AC:

1890

AN:

10580

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13616

AN:

67990

Other (OTH)

AF:

0.281

AC:

592

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1479

2958

4436

5915

7394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

1317

Bravo

AF:

0.274

Asia WGS

AF:

0.432

AC:

1499

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.7

(source)

DANN

Benign

0.59

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over