5-159315006-G-T

Position:

• chr5-159315006-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000231228.3(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 ENST00000231228.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209

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]

LOC105377683 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12B	NM_002187.3	c.*1095C>A		3_prime_UTR_variant	8/8	ENST00000231228.3	NP_002178.2
LOC105377683	XR_941138.3	n.401-212G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.*1095C>A		3_prime_UTR_variant	8/8	1	NM_002187.3	ENSP00000231228	P1
IL12B	ENST00000696750.1	c.*1095C>A		3_prime_UTR_variant	5/5			ENSP00000512849
IL12B	ENST00000696751.1	c.*1577C>A		3_prime_UTR_variant, NMD_transcript_variant	7/7			ENSP00000512850
	ENST00000521472.6	n.289+3592G>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 EAS exome AF: 0.851

Gnomad4 NFE exome AF: 0.750

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

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.882

Alfa AF: 0.841 Hom.: 20223

Bravo AF: 0.881

Asia WGS AF: 0.942 AC: 3278 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs1368439; hg19: chr5-158742014;