rs730690

Variant names:

• chr5-159329158-G-A
• rs730690
• NM_002187.3:c.-1+1274C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002187.3(IL12B):​c.-1+1274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,022 control chromosomes in the GnomAD database, including 5,421 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 (5421 hom., cov: 32)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 11 publications found

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)

ENSG00000249738 (HGNC:58156):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3	c.-1+1274C>T		intron_variant	Intron 1 of 7	ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.-1+1274C>T		intron_variant	Intron 1 of 7	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38887 AN: 151904 Hom.: 5417 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.256 AC: 38913 AN: 152022 Hom.: 5421 Cov.: 32 AF XY: 0.261 AC XY: 19367 AN XY: 74312

African (AFR) AF: 0.316 AC: 13102 AN: 41446

American (AMR) AF: 0.320 AC: 4893 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2392 AN: 5166

South Asian (SAS) AF: 0.320 AC: 1539 AN: 4810

European-Finnish (FIN) AF: 0.207 AC: 2189 AN: 10568

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13400 AN: 67970

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.256 Hom.: 1225

Bravo AF: 0.269

Asia WGS AF: 0.428 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs730690; hg19: chr5-158756166;