3-159994271-A-G

Variant names:

• chr3-159994271-A-G
• rs2243131
• NM_001397992.1:c.504+427A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001397992.1(IL12A):​c.504+427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL12A NM_001397992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397992.1. 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.504+427A>G		intron	N/A	NP_001384921.1
	IL12A-AS1	NR_108088.1		n.1119T>C		non_coding_transcript_exon	Exon 8 of 10
	IL12A	NM_000882.4		c.606+427A>G		intron	N/A	NP_000873.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000699704.1	MANE Select	c.504+427A>G		intron	N/A	ENSP00000514529.1
	IL12A	ENST00000305579.7	TSL:1	c.606+427A>G		intron	N/A	ENSP00000303231.2
	IL12A-AS1	ENST00000497452.5	TSL:2	n.1119T>C		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4892 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2496

African (AFR) AF: 0.00 AC: 0 AN: 78

American (AMR) AF: 0.00 AC: 0 AN: 1042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 76

East Asian (EAS) AF: 0.00 AC: 0 AN: 272

South Asian (SAS) AF: 0.00 AC: 0 AN: 320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 64

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2840

Other (OTH) AF: 0.00 AC: 0 AN: 196

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1615

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.070
DANN	Benign	0.50
PhyloP100		-1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2243131; hg19: chr3-159712058;