rs2227314

Positions:

• chr3-159994267-G-T

Variant summary

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

The NM_000882.4(IL12A):​c.606+423G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 156,548 control chromosomes in the GnomAD database, including 26,178 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 0.58 (25568 hom., cov: 31)
  • Exomes 𝑓: 0.50 (610 hom.)
• Consequence: IL12A NM_000882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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-AS1 (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 (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12A	NM_000882.4	c.606+423G>T		intron_variant			NP_000873.2
IL12A	NM_001354582.2	c.564+423G>T		intron_variant			NP_001341511.1
IL12A	NM_001397992.1	c.504+423G>T		intron_variant			NP_001384921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1	c.504+423G>T		intron_variant				ENSP00000514529.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87415 AN: 151816 Hom.: 25542 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.500 AC: 2308 AN: 4614 Hom.: 610 Cov.: 0 AF XY: 0.494 AC XY: 1169 AN XY: 2368

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.576 AC: 87498 AN: 151934 Hom.: 25568 Cov.: 31 AF XY: 0.570 AC XY: 42363 AN XY: 74260

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.547

Alfa AF: 0.598 Hom.: 3646

Bravo AF: 0.577

Asia WGS AF: 0.486 AC: 1691 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	2.0
DANN	Benign	0.29

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: rs2227314; hg19: chr3-159712054;