dbSNP rs3212217: IL12B:c.1-1340G>C (chr5-159328122-C-G) – 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.1-1340G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,074 control chromosomes in the GnomAD database, including 5,769 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 ( 5769 hom., cov: 32)

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.519

Publications

43 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3 link	c.1-1340G>C		intron_variant	Intron 1 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.1-1340G>C		intron_variant	Intron 1 of 7	1	NM_002187.3	ENSP00000231228.2		P29460

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39998

AN:

151956

Hom.:

5763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.279

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

GnomAD4 genome

AF:

0.263

AC:

40026

AN:

152074

Hom.:

5769

Cov.:

AF XY:

0.268

AC XY:

19928

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.324

AC:

13434

AN:

41450

American (AMR)

AF:

0.332

AC:

5071

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

591

AN:

3470

East Asian (EAS)

AF:

0.476

AC:

2455

AN:

5160

South Asian (SAS)

AF:

0.360

AC:

1738

AN:

4822

European-Finnish (FIN)

AF:

0.209

AC:

2217

AN:

10584

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13665

AN:

67984

Other (OTH)

AF:

0.281

AC:

593

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1475

2950

4425

5900

7375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.224

Hom.:

617

Bravo

AF:

0.276

Asia WGS

AF:

0.441

AC:

1529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.84

(source)

DANN

Benign

0.35

PhyloP100

-0.52

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