rs2243123

Positions:

• chr3-159991864-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000882.4(IL12A):​c.265-1148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,166 control chromosomes in the GnomAD database, including 4,636 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 0.24 (4636 hom., cov: 32)
• Consequence: IL12A NM_000882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

IL12A (HGNC:5969): (interleukin 12A) This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]

IL12A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12A	NM_000882.4	c.265-1148T>C		intron_variant			NP_000873.2
IL12A	NM_001354582.2	c.265-1148T>C		intron_variant			NP_001341511.1
IL12A	NM_001397992.1	c.163-1148T>C		intron_variant			NP_001384921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1	c.163-1148T>C		intron_variant				ENSP00000514529.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36473 AN: 152048 Hom.: 4637 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.240 AC: 36489 AN: 152166 Hom.: 4636 Cov.: 32 AF XY: 0.235 AC XY: 17495 AN XY: 74394

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0828

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.252

Alfa AF: 0.270 Hom.: 7752

Bravo AF: 0.247

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2243123; hg19: chr3-159709651;