dbSNP rs2243123: IL12A:c.163-1148T>C (chr3-159991864-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001397992.1(IL12A):c.163-1148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,166 control chromosomes in the GnomAD database, including 4,636 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 0.24 ( 4636 hom., cov: 32)

Consequence

IL12A
NM_001397992.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

57 publications found

Variant links:

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 links:

IL12A-AS1 (HGNC:49094): (IL12A antisense RNA 1)

IL12A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL12A	NM_001397992.1	MANE Select	c.163-1148T>C	intron	N/A	NP_001384921.1	P29459
IL12A	NM_000882.4		c.265-1148T>C	intron	N/A	NP_000873.2
IL12A	NM_001354582.2		c.265-1148T>C	intron	N/A	NP_001341511.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL12A	ENST00000699704.1	MANE Select	c.163-1148T>C	intron	N/A	ENSP00000514529.1	P29459
IL12A	ENST00000305579.7	TSL:1	c.265-1148T>C	intron	N/A	ENSP00000303231.2	O60595
IL12A	ENST00000466512.1	TSL:3	c.163-1148T>C	intron	N/A	ENSP00000419046.2	E9PGR3

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36473

AN:

152048

Hom.:

4637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0828

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.240

AC:

36489

AN:

152166

Hom.:

4636

Cov.:

AF XY:

0.235

AC XY:

17495

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.173

AC:

7196

AN:

41530

American (AMR)

AF:

0.283

AC:

4325

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3472

East Asian (EAS)

AF:

0.0828

AC:

429

AN:

5180

South Asian (SAS)

AF:

0.112

AC:

542

AN:

4824

European-Finnish (FIN)

AF:

0.272

AC:

2875

AN:

10582

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19498

AN:

67978

Other (OTH)

AF:

0.252

AC:

532

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1405

2809

4214

5618

7023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.267

Hom.:

17880

Bravo

AF:

0.247

Asia WGS

AF:

0.0980

AC:

342

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over