rs1368439

Variant names:

• chr5-159315006-G-T
• rs1368439
• NM_002187.3:c.*1095C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-159315006-G-T
• chr5-159315006-G-A
• chr5-159315006-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002187.3(IL12B):​c.*1095C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,324 control chromosomes in the GnomAD database, including 58,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (58171 hom., cov: 30)
  • Exomes 𝑓: 0.85 (41 hom.)
• Consequence: IL12B NM_002187.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209
• Publications: 32 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):

LOC105377683 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-159315006-G-T is Benign according to our data. Variant chr5-159315006-G-T is described in ClinVar as Benign. ClinVar VariationId is 352554.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.*1095C>A		3_prime_UTR	Exon 8 of 8	NP_002178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	ENST00000231228.3	TSL:1 MANE Select	c.*1095C>A		3_prime_UTR	Exon 8 of 8	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.*1095C>A		3_prime_UTR	Exon 5 of 5	ENSP00000512849.1	A0A8Q3WML5
	IL12B	ENST00000696751.1		n.*1577C>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000512850.1	A0A8Q3SJ12

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132689 AN: 152088 Hom.: 58109 Cov.: 30

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.881

GnomAD4 exome AF: 0.847 AC: 100 AN: 118 Hom.: 41 Cov.: 0 AF XY: 0.843 AC XY: 59 AN XY: 70

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.851 AC: 97 AN: 114

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.873 AC: 132811 AN: 152206 Hom.: 58171 Cov.: 30 AF XY: 0.876 AC XY: 65195 AN XY: 74400

African (AFR) AF: 0.944 AC: 39236 AN: 41542

American (AMR) AF: 0.896 AC: 13703 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5164 AN: 5172

South Asian (SAS) AF: 0.868 AC: 4190 AN: 4826

European-Finnish (FIN) AF: 0.858 AC: 9087 AN: 10590

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55628 AN: 67998

Other (OTH) AF: 0.882 AC: 1860 AN: 2110

Alfa AF: 0.849 Hom.: 34166

Bravo AF: 0.881

Asia WGS AF: 0.942 AC: 3278 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-0.21
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: rs1368439; hg19: chr5-158742014;