rs6894567

Variant names:

• chr5-159329960-A-G
• rs6894567
• NM_002187.3:c.-1+472T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-159329960-A-G
• chr5-159329960-A-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+472T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,976 control chromosomes in the GnomAD database, including 5,463 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 (5463 hom., cov: 32)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 18 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 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+472T>C		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+472T>C		intron	N/A	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.-149+472T>C		intron	N/A	ENSP00000512849.1	A0A8Q3WML5
	IL12B-AS1	ENST00000521472.6	TSL:3	n.411-2822A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38993 AN: 151860 Hom.: 5459 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.257 AC: 39017 AN: 151976 Hom.: 5463 Cov.: 32 AF XY: 0.262 AC XY: 19439 AN XY: 74288

African (AFR) AF: 0.316 AC: 13101 AN: 41410

American (AMR) AF: 0.321 AC: 4898 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.468 AC: 2415 AN: 5156

South Asian (SAS) AF: 0.330 AC: 1587 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2173 AN: 10560

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13440 AN: 67994

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

Alfa AF: 0.242 Hom.: 2416

Bravo AF: 0.270

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		-0.059
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: rs6894567; hg19: chr5-158756968;