rs1433048

Variant names:

• chr5-159328837-G-A
• rs1433048
• NM_002187.3:c.-1+1595C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-159328837-G-A
• chr5-159328837-G-C
• chr5-159328837-G-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+1595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,138 control chromosomes in the GnomAD database, including 57,626 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 0.87 (57626 hom., cov: 31)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 24 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

IL12B-AS1 (HGNC:58156):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	NM_002187.3	MANE Select	c.-1+1595C>T		intron	N/A	NP_002178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	ENST00000231228.3	TSL:1 MANE Select	c.-1+1595C>T		intron	N/A	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.-149+1595C>T		intron	N/A	ENSP00000512849.1	A0A8Q3WML5
	IL12B-AS1	ENST00000521472.6	TSL:3	n.410+3183G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131918 AN: 152020 Hom.: 57565 Cov.: 31

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.868 AC: 132039 AN: 152138 Hom.: 57626 Cov.: 31 AF XY: 0.867 AC XY: 64492 AN XY: 74364

African (AFR) AF: 0.956 AC: 39687 AN: 41516

American (AMR) AF: 0.898 AC: 13724 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5158 AN: 5166

South Asian (SAS) AF: 0.870 AC: 4188 AN: 4814

European-Finnish (FIN) AF: 0.761 AC: 8050 AN: 10578

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55398 AN: 67986

Other (OTH) AF: 0.883 AC: 1866 AN: 2114

Alfa AF: 0.837 Hom.: 43489

Bravo AF: 0.885

Asia WGS AF: 0.949 AC: 3301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		0.23
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: rs1433048; hg19: chr5-158755845;