5-159315199-AT-A

Position:

• chr5-159315199-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002187.3(IL12B):​c.*901delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 147,178 control chromosomes in the GnomAD database, including 1,914 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1914 hom., cov: 29)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: IL12B NM_002187.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.466

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]

ENSG00000249738 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-159315199-AT-A is Benign according to our data. Variant chr5-159315199-AT-A is described in ClinVar as [Benign]. Clinvar id is 352559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12B	NM_002187.3	c.*901delA		3_prime_UTR_variant	8/8	ENST00000231228.3	NP_002178.2
LOC105377683	XR_941138.3	n.401-8delT		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228	c.*901delA		3_prime_UTR_variant	8/8	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22092 AN: 146968 Hom.: 1899 Cov.: 29

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.100 AC: 13 AN: 130 Hom.: 0 Cov.: 0 AF XY: 0.0952 AC XY: 8 AN XY: 84

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.0638

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.151 AC: 22139 AN: 147048 Hom.: 1914 Cov.: 29 AF XY: 0.146 AC XY: 10424 AN XY: 71494

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0420

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.156

Alfa AF: 0.0450 Hom.: 40

Bravo AF: 0.158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial Atypical Mycobacteriosis, Autosomal Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs34324765; hg19: chr5-158742207;