chr3-159993805-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000305579.7(IL12A):c.567A>G(p.Leu189Leu) 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
ENST00000305579.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0440

Publications

1 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 -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 CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id is 729130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-159993805-A-G is described in CliVar as Benign. Clinvar id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
IL12A	NM_000882.4 link	c.567A>G	p.Leu189Leu	synonymous_variant	Exon 6 of 7	NP_000873.2	P29459O60595
IL12A	NM_001354582.2 link	c.525A>G	p.Leu175Leu	synonymous_variant	Exon 5 of 6	NP_001341511.1
IL12A	NM_001397992.1 link	c.465A>G	p.Leu155Leu	synonymous_variant	Exon 6 of 7	NP_001384921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1 link	c.465A>G	p.Leu155Leu	synonymous_variant	Exon 6 of 7			ENSP00000514529.1		P29459

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152232

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.000304

AC XY:

221

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0124

AC:

414

AN:

33480

American (AMR)

AF:

0.000492

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111978

Other (OTH)

AF:

0.00106

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00314

AC:

478

AN:

152350

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0108

AC:

449

AN:

41576

American (AMR)

AF:

0.00131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00377

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

(source)

DANN

Benign

0.62

PhyloP100

0.044

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over