rs2243131

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-159994271-A-C
• chr3-159994271-A-G

Variant summary

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

The NM_001397992.1(IL12A):​c.504+427A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 156,984 control chromosomes in the GnomAD database, including 2,792 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 0.18 (2743 hom., cov: 32)
  • Exomes 𝑓: 0.13 (49 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	NM_001397992.1	MANE Select	c.504+427A>C		intron	N/A	NP_001384921.1	P29459
	IL12A	NM_000882.4		c.606+427A>C		intron	N/A	NP_000873.2
	IL12A	NM_001354582.2		c.564+427A>C		intron	N/A	NP_001341511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000699704.1	MANE Select	c.504+427A>C		intron	N/A	ENSP00000514529.1	P29459
	IL12A	ENST00000305579.7	TSL:1	c.606+427A>C		intron	N/A	ENSP00000303231.2	O60595
	IL12A	ENST00000466512.1	TSL:3	c.462+427A>C		intron	N/A	ENSP00000419046.2	E9PGR3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27670 AN: 151978 Hom.: 2741 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.128 AC: 628 AN: 4888 Hom.: 49 Cov.: 0 AF XY: 0.122 AC XY: 303 AN XY: 2492

African (AFR) AF: 0.128 AC: 10 AN: 78

American (AMR) AF: 0.0691 AC: 72 AN: 1042

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 15 AN: 76

East Asian (EAS) AF: 0.0772 AC: 21 AN: 272

South Asian (SAS) AF: 0.269 AC: 86 AN: 320

European-Finnish (FIN) AF: 0.125 AC: 8 AN: 64

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

European-Non Finnish (NFE) AF: 0.139 AC: 395 AN: 2836

Other (OTH) AF: 0.107 AC: 21 AN: 196

GnomAD4 genome AF: 0.182 AC: 27708 AN: 152096 Hom.: 2743 Cov.: 32 AF XY: 0.184 AC XY: 13677 AN XY: 74344

African (AFR) AF: 0.223 AC: 9266 AN: 41490

American (AMR) AF: 0.114 AC: 1742 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3468

East Asian (EAS) AF: 0.129 AC: 667 AN: 5178

South Asian (SAS) AF: 0.337 AC: 1620 AN: 4806

European-Finnish (FIN) AF: 0.154 AC: 1630 AN: 10586

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11388 AN: 67982

Other (OTH) AF: 0.164 AC: 345 AN: 2108

Alfa AF: 0.168 Hom.: 1615

Bravo AF: 0.174

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.064
DANN	Benign	0.52
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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;