rs568408

Positions:

• chr3-159995680-G-A

Variant summary

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

The NM_000882.4(IL12A):​c.*121G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 603,328 control chromosomes in the GnomAD database, including 7,561 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 0.16 (2025 hom., cov: 32)
  • Exomes 𝑓: 0.15 (5536 hom.)
• Consequence: IL12A NM_000882.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL12A	NM_001397992.1	c.*121G>A		3_prime_UTR_variant	7/7	ENST00000699704.1	NP_001384921.1
IL12A	NM_000882.4	c.*121G>A		3_prime_UTR_variant	7/7		NP_000873.2
IL12A-AS1	NR_108088.1	n.1085-1375C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1	c.*121G>A		3_prime_UTR_variant	7/7		NM_001397992.1	ENSP00000514529	P1
IL12A-AS1	ENST00000497452.5	n.1085-1375C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23656 AN: 151960 Hom.: 2025 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.148 AC: 66864 AN: 451250 Hom.: 5536 Cov.: 6 AF XY: 0.153 AC XY: 36058 AN XY: 235316

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.156 AC: 23681 AN: 152078 Hom.: 2025 Cov.: 32 AF XY: 0.158 AC XY: 11740 AN XY: 74344

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0859

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.128

Alfa AF: 0.140 Hom.: 1392

Bravo AF: 0.145

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.50

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: rs568408; hg19: chr3-159713467; COSMIC: COSV59759097; COSMIC: COSV59759097;