rs568408

Variant names:

• chr3-159995680-G-A
• rs568408
• NM_001397992.1:c.*121G>A

Variant summary

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

The NM_001397992.1(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_001397992.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 123 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 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.*121G>A		3_prime_UTR	Exon 7 of 7	NP_001384921.1	P29459
	IL12A	NM_000882.4		c.*121G>A		3_prime_UTR	Exon 7 of 7	NP_000873.2
	IL12A	NM_001354582.2		c.*121G>A		3_prime_UTR	Exon 6 of 6	NP_001341511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000699704.1	MANE Select	c.*121G>A		3_prime_UTR	Exon 7 of 7	ENSP00000514529.1	P29459
	IL12A	ENST00000305579.7	TSL:1	c.*121G>A		3_prime_UTR	Exon 7 of 7	ENSP00000303231.2	O60595
	IL12A	ENST00000466512.1	TSL:3	c.*121G>A		3_prime_UTR	Exon 6 of 6	ENSP00000419046.2	E9PGR3

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

African (AFR) AF: 0.194 AC: 2194 AN: 11284

American (AMR) AF: 0.0625 AC: 1068 AN: 17078

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1354 AN: 12142

East Asian (EAS) AF: 0.114 AC: 3265 AN: 28602

South Asian (SAS) AF: 0.320 AC: 7660 AN: 23944

European-Finnish (FIN) AF: 0.151 AC: 5546 AN: 36712

Middle Eastern (MID) AF: 0.137 AC: 462 AN: 3376

European-Non Finnish (NFE) AF: 0.142 AC: 41790 AN: 293614

Other (OTH) AF: 0.144 AC: 3525 AN: 24498

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

African (AFR) AF: 0.192 AC: 7961 AN: 41486

American (AMR) AF: 0.0859 AC: 1312 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3466

East Asian (EAS) AF: 0.129 AC: 668 AN: 5178

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4816

European-Finnish (FIN) AF: 0.148 AC: 1563 AN: 10548

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9838 AN: 67990

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.146 Hom.: 4116

Bravo AF: 0.145

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-1.7
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: rs568408; hg19: chr3-159713467; COSMIC: COSV59759097; COSMIC: COSV59759097;