rs3181219

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_002187.3(IL12B):c.88+1564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0831 (AC=12,643) in the gnomAD database across 152,226 control chromosomes, including 664 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.128. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.083 ( 664 hom., cov: 32)

Consequence

IL12B
NM_002187.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

10 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

IL12B links:

IL12B-AS1 (HGNC:58156):

IL12B-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002187.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1275 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002187.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	NM_002187.3	MANE Select	c.88+1564G>A		intron	N/A	NP_002178.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL12B	ENST00000231228.3	TSL:1 MANE Select	c.88+1564G>A	intron	N/A	ENSP00000231228.2	P29460
IL12B	ENST00000696750.1		c.-148-4611G>A	intron	N/A	ENSP00000512849.1	A0A8Q3WML5
IL12B-AS1	ENST00000765006.1		n.549C>T	non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.0831

AC:

12639

AN:

152106

Hom.:

660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0395

Gnomad SAS

AF:

0.0644

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.102

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

GnomAD4 genome

AF:

0.0831

AC:

12643

AN:

152226

Hom.:

664

Cov.:

AF XY:

0.0808

AC XY:

6013

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0233

AC:

970

AN:

41548

American (AMR)

AF:

0.132

AC:

2023

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

624

AN:

3468

East Asian (EAS)

AF:

0.0396

AC:

205

AN:

5176

South Asian (SAS)

AF:

0.0643

AC:

310

AN:

4824

European-Finnish (FIN)

AF:

0.0708

AC:

751

AN:

10604

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7408

AN:

67996

Other (OTH)

AF:

0.101

AC:

213

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

593

1185

1778

2370

2963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.0889

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.102

AC:

5068

AN:

49748

Hom.:

315

Local populations

ABraOM SABE-WGS-1171

AF:

0.101

AC:

236

AN:

2342

Hom.:

ChinaMAP Phase 1

AF:

0.0508

Denmark Genome

AF:

0.0600

AC:

AN:

300

GenomeAsia100K

AF:

0.0520

AC:

179

AN:

3478

show subpopulations

Oceania

AF:

0.00676

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.0470

AC:

AN:

702

Hom.:

South-East Asia

AF:

0.0477

AC:

AN:

692

Hom.:

South Asia

AF:

0.0470

AC:

AN:

1448

Hom.:

Africa

AF:

0.0192

AC:

AN:

208

Hom.:

America

AF:

0.308

AC:

AN:

Hom.:

West Eurasia

AF:

0.105

AC:

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.0480

AC:

346

AN:

7234

Qatari Genome

AF:

0.193

AC:

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0316

AC:

3881

AN:

122642

Hom.:

Turkish Variome

AF:

0.129

AC:

200

AN:

1546

Hom.:

UK10K

AF:

0.110

AC:

829

AN:

7562

show subpopulations

TwinsUK

AF:

0.108

AC:

387

AN:

3574

ALSPAC

AF:

0.111

AC:

427

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0551

AC:

494

AN:

8960

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

(source)

DANN

Benign

0.50

PhyloP100

-1.2

AlphaGenome AVI

Benign

5.7

(source)

GPN-Star LLR

0.061

(source)

GPN-Star score

-0.061

(source)

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

Pangolin (max)

Benign

0.0

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over