rs2230052

Variant names:

• chr3-159993805-A-G
• rs2230052
• NM_001397992.1:c.465A>G
• IL12A p.Leu155Leu

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001397992.1(IL12A):​c.465A>G​(p.Leu155Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000624 in 1,614,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (3 hom.)
• Consequence: IL12A NM_001397992.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-159993805-A-G is Benign according to our data. Variant chr3-159993805-A-G is described in ClinVar as Benign. ClinVar VariationId is 729130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.044 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.465A>G	p.Leu155Leu	synonymous	Exon 6 of 7	NP_001384921.1	P29459
	IL12A	NM_000882.4		c.567A>G	p.Leu189Leu	synonymous	Exon 6 of 7	NP_000873.2
	IL12A	NM_001354582.2		c.525A>G	p.Leu175Leu	synonymous	Exon 5 of 6	NP_001341511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000699704.1	MANE Select	c.465A>G	p.Leu155Leu	synonymous	Exon 6 of 7	ENSP00000514529.1	P29459
	IL12A	ENST00000305579.7	TSL:1	c.567A>G	p.Leu189Leu	synonymous	Exon 6 of 7	ENSP00000303231.2	O60595
	IL12A	ENST00000466512.1	TSL:3	c.423A>G	p.Leu141Leu	synonymous	Exon 5 of 6	ENSP00000419046.2	E9PGR3

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000887 AC: 223 AN: 251398 AF XY: 0.000640

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000362 AC: 529 AN: 1461852 Hom.: 3 Cov.: 31 AF XY: 0.000304 AC XY: 221 AN XY: 727228

African (AFR) AF: 0.0124 AC: 414 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111978

Other (OTH) AF: 0.00106 AC: 64 AN: 60396

GnomAD4 genome AF: 0.00314 AC: 478 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.00283 AC XY: 211 AN XY: 74512

African (AFR) AF: 0.0108 AC: 449 AN: 41576

American (AMR) AF: 0.00131 AC: 20 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00172 Hom.: 1

Bravo AF: 0.00377

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.62
PhyloP100		0.044
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230052;

hg19: chr3-159711592;