rs583911

Variant names:

• chr3-159992603-G-A
• rs583911
• ENST00000305579.7:c.265-409G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000305579.7(IL12A):​c.265-409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,010 control chromosomes in the GnomAD database, including 29,905 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 0.61 (29905 hom., cov: 32)
• Consequence: IL12A ENST00000305579.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 44 publications found

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:49094): (IL12A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL12A	NM_000882.4	c.265-409G>A		intron_variant	Intron 2 of 6		NP_000873.2
IL12A	NM_001354582.2	c.265-409G>A		intron_variant	Intron 2 of 5		NP_001341511.1
IL12A	NM_001397992.1	c.163-409G>A		intron_variant	Intron 2 of 6		NP_001384921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1	c.163-409G>A		intron_variant	Intron 2 of 6			ENSP00000514529.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93348 AN: 151892 Hom.: 29862 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.615 AC: 93451 AN: 152010 Hom.: 29905 Cov.: 32 AF XY: 0.608 AC XY: 45165 AN XY: 74282

African (AFR) AF: 0.803 AC: 33290 AN: 41464

American (AMR) AF: 0.508 AC: 7758 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1515 AN: 5166

South Asian (SAS) AF: 0.574 AC: 2762 AN: 4816

European-Finnish (FIN) AF: 0.533 AC: 5614 AN: 10538

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38686 AN: 67964

Other (OTH) AF: 0.573 AC: 1207 AN: 2108

Alfa AF: 0.589 Hom.: 13610

Bravo AF: 0.619

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		0.24
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: rs583911; hg19: chr3-159710390;