Genetic Variant IL12B:c.*901delA (chr5-159315199-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002187.3(IL12B):c.*901delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 147,178 control chromosomes in the GnomAD database, including 1,914 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1914 hom., cov: 29)

Exomes 𝑓: 0.10 ( 0 hom. )

Consequence

IL12B
NM_002187.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.466

Publications

1 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:

LOC105377683 (HGNC:):

LOC105377683 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3 link	c.*901delA		3_prime_UTR_variant	Exon 8 of 8	ENST00000231228.3	NP_002178.2	P29460
LOC105377683	XR_941138.3 link	n.401-8delT		splice_region_variant, intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3 link	c.*901delA		3_prime_UTR_variant	Exon 8 of 8	1	NM_002187.3	ENSP00000231228.2		P29460

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22092

AN:

146968

Hom.:

1899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.0813

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.100

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.0952

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0638

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.231

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.151

AC:

22139

AN:

147048

Hom.:

1914

Cov.:

AF XY:

0.146

AC XY:

10424

AN XY:

71494

show subpopulations

African (AFR)

AF:

0.246

AC:

9947

AN:

40390

American (AMR)

AF:

0.156

AC:

2308

AN:

14754

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

635

AN:

3420

East Asian (EAS)

AF:

0.0420

AC:

212

AN:

5050

South Asian (SAS)

AF:

0.0683

AC:

315

AN:

4614

European-Finnish (FIN)

AF:

0.0813

AC:

748

AN:

9200

Middle Eastern (MID)

AF:

0.187

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.113

AC:

7511

AN:

66396

Other (OTH)

AF:

0.156

AC:

318

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

903

1805

2708

3610

4513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0450

Hom.:

Bravo

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial Atypical Mycobacteriosis, Autosomal Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.47

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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chr5-159315199-AT-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over