dbSNP rs2243131: IL12A:c.606+427A>C (chr3-159994271-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000305579.7(IL12A):c.606+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
ENST00000305579.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

Publications

15 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:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL12A-AS1	NR_108088.1 link	n.1119T>G	non_coding_transcript_exon_variant	Exon 8 of 10
IL12A	NM_000882.4 link	c.606+427A>C	intron_variant	Intron 6 of 6	NP_000873.2	P29459O60595
IL12A	NM_001354582.2 link	c.564+427A>C	intron_variant	Intron 5 of 5	NP_001341511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1 link	c.504+427A>C		intron_variant	Intron 6 of 6			ENSP00000514529.1		P29459

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27670

AN:

151978

Hom.:

2741

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.122

AC XY:

303

AN XY:

2492

show subpopulations

African (AFR)

AF:

0.128

AC:

AN:

American (AMR)

AF:

0.0691

AC:

AN:

1042

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

AN:

East Asian (EAS)

AF:

0.0772

AC:

AN:

272

South Asian (SAS)

AF:

0.269

AC:

AN:

320

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.139

AC:

395

AN:

2836

Other (OTH)

AF:

0.107

AC:

AN:

196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.182

AC:

27708

AN:

152096

Hom.:

2743

Cov.:

AF XY:

0.184

AC XY:

13677

AN XY:

74344

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11388

AN:

67982

Other (OTH)

AF:

0.164

AC:

345

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1140

2280

3419

4559

5699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.168

Hom.:

1615

Bravo

AF:

0.174

Asia WGS

AF:

0.262

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.064

(source)

DANN

Benign

0.52

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over