chr5-159320556-A-C

Variant names:

• chr5-159320556-A-C
• rs919766
• NM_002187.3:c.483-36T>G

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.483-36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,547,022 control chromosomes in the GnomAD database, including 11,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9562 hom.)
• Consequence: IL12B NM_002187.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.248
• Publications: 35 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000249738 (HGNC:58156):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-159320556-A-C is Benign according to our data. Variant chr5-159320556-A-C is described in ClinVar as Benign. ClinVar VariationId is 2628262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12B	NM_002187.3	c.483-36T>G		intron_variant	Intron 4 of 7	ENST00000231228.3	NP_002178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12B	ENST00000231228.3	c.483-36T>G		intron_variant	Intron 4 of 7	1	NM_002187.3	ENSP00000231228.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21409 AN: 152126 Hom.: 1796 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.119 AC: 29470 AN: 247156 AF XY: 0.114

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0460

Gnomad FIN exome AF: 0.0726

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.111 AC: 155515 AN: 1394778 Hom.: 9562 Cov.: 23 AF XY: 0.110 AC XY: 76610 AN XY: 697870

African (AFR) AF: 0.224 AC: 7182 AN: 32054

American (AMR) AF: 0.188 AC: 8349 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4542 AN: 25712

East Asian (EAS) AF: 0.0415 AC: 1633 AN: 39360

South Asian (SAS) AF: 0.0715 AC: 6058 AN: 84696

European-Finnish (FIN) AF: 0.0719 AC: 3822 AN: 53140

Middle Eastern (MID) AF: 0.178 AC: 861 AN: 4846

European-Non Finnish (NFE) AF: 0.110 AC: 116180 AN: 1052504

Other (OTH) AF: 0.119 AC: 6888 AN: 58044

GnomAD4 genome AF: 0.141 AC: 21455 AN: 152244 Hom.: 1811 Cov.: 32 AF XY: 0.136 AC XY: 10140 AN XY: 74432

African (AFR) AF: 0.223 AC: 9250 AN: 41516

American (AMR) AF: 0.151 AC: 2305 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3470

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5172

South Asian (SAS) AF: 0.0650 AC: 314 AN: 4832

European-Finnish (FIN) AF: 0.0711 AC: 755 AN: 10618

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7533 AN: 68012

Other (OTH) AF: 0.147 AC: 311 AN: 2114

Alfa AF: 0.134 Hom.: 571

Bravo AF: 0.153

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.48
PhyloP100		-0.25
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: rs919766; hg19: chr5-158747564;