dbSNP rs2227314: IL12A:c.606+423G>T (chr3-159994267-G-T) – 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+423G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 156,548 control chromosomes in the GnomAD database, including 26,178 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 0.58 ( 25568 hom., cov: 31)

Exomes 𝑓: 0.50 ( 610 hom. )

Consequence

IL12A
ENST00000305579.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

Publications

9 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
IL12A-AS1	NR_108088.1 link	n.1123C>A	non_coding_transcript_exon_variant	Exon 8 of 10
IL12A	NM_000882.4 link	c.606+423G>T	intron_variant	Intron 6 of 6	NP_000873.2	P29459O60595
IL12A	NM_001354582.2 link	c.564+423G>T	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+423G>T		intron_variant	Intron 6 of 6			ENSP00000514529.1		P29459

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87415

AN:

151816

Hom.:

25542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.667

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.500

AC:

2308

AN:

4614

Hom.:

610

Cov.:

AF XY:

0.494

AC XY:

1169

AN XY:

2368

show subpopulations

African (AFR)

AF:

0.614

AC:

AN:

American (AMR)

AF:

0.444

AC:

400

AN:

900

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

AN:

East Asian (EAS)

AF:

0.252

AC:

AN:

282

South Asian (SAS)

AF:

0.550

AC:

154

AN:

280

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.300

AC:

AN:

European-Non Finnish (NFE)

AF:

0.535

AC:

1439

AN:

2688

Other (OTH)

AF:

0.495

AC:

104

AN:

210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

126

189

252

315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.576

AC:

87498

AN:

151934

Hom.:

25568

Cov.:

AF XY:

0.570

AC XY:

42363

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.667

AC:

27613

AN:

41412

American (AMR)

AF:

0.498

AC:

7606

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1952

AN:

3468

East Asian (EAS)

AF:

0.292

AC:

1508

AN:

5166

South Asian (SAS)

AF:

0.573

AC:

2758

AN:

4810

European-Finnish (FIN)

AF:

0.532

AC:

5615

AN:

10554

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38627

AN:

67940

Other (OTH)

AF:

0.547

AC:

1151

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.601

Hom.:

3838

Bravo

AF:

0.577

Asia WGS

AF:

0.486

AC:

1691

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

(source)

DANN

Benign

0.29

PhyloP100

-0.068

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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