ENST00000305579.7:c.265-701A>C

Variant names:

• chr3-159992311-A-C
• rs582537
• NM_001397992.1:c.163-701A>C

Variant summary

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

The ENST00000305579.7(IL12A):​c.265-701A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,938 control chromosomes in the GnomAD database, including 26,699 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 0.59 (26699 hom., cov: 31)
• Consequence: IL12A ENST00000305579.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305579.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	NM_001397992.1	MANE Select	c.163-701A>C		intron	N/A	NP_001384921.1
	IL12A	NM_000882.4		c.265-701A>C		intron	N/A	NP_000873.2
	IL12A	NM_001354582.2		c.265-701A>C		intron	N/A	NP_001341511.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000699704.1	MANE Select	c.163-701A>C		intron	N/A	ENSP00000514529.1
	IL12A	ENST00000305579.7	TSL:1	c.265-701A>C		intron	N/A	ENSP00000303231.2
	IL12A	ENST00000466512.1	TSL:3	c.163-701A>C		intron	N/A	ENSP00000419046.2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89068 AN: 151820 Hom.: 26670 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.587 AC: 89154 AN: 151938 Hom.: 26699 Cov.: 31 AF XY: 0.581 AC XY: 43149 AN XY: 74268

African (AFR) AF: 0.703 AC: 29111 AN: 41420

American (AMR) AF: 0.502 AC: 7676 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1520 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2758 AN: 4808

European-Finnish (FIN) AF: 0.533 AC: 5617 AN: 10532

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38672 AN: 67946

Other (OTH) AF: 0.559 AC: 1178 AN: 2108

Alfa AF: 0.543 Hom.: 3825

Bravo AF: 0.589

Asia WGS AF: 0.490 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		0.20
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: rs582537; hg19: chr3-159710098;