Variant 3-159995456-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000882.4(IL12A):c.659C>T(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,607,448 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 2 hom. )

Consequence

IL12A
NM_000882.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.454

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 (HGNC:):

IL12A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057649314).

BP6

Variant 3-159995456-C-T is Benign according to our data. Variant chr3-159995456-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
IL12A	NM_000882.4 linkuse as main transcript	c.659C>T	p.Pro220Leu	missense_variant	7/7	NP_000873.2	P29459O60595
IL12A	NM_001354582.2 linkuse as main transcript	c.617C>T	p.Pro206Leu	missense_variant	6/6	NP_001341511.1
IL12A	NM_001397992.1 linkuse as main transcript	c.557C>T	p.Pro186Leu	missense_variant	7/7	NP_001384921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL12A	ENST00000699704.1 linkuse as main transcript	c.557C>T	p.Pro186Leu	missense_variant	7/7			ENSP00000514529.1		P29459

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000761

AC:

187

AN:

245812

Hom.:

AF XY:

0.000715

AC XY:

AN XY:

132912

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000399

Gnomad ASJ exome

AF:

0.00469

Gnomad EAS exome

AF:

0.00282

Gnomad SAS exome

AF:

0.000137

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000604

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000739

AC:

1075

AN:

1455144

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

518

AN XY:

723836

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.00453

Gnomad4 EAS exome

AF:

0.00369

Gnomad4 SAS exome

AF:

0.000142

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000669

Gnomad4 OTH exome

AF:

0.000682

GnomAD4 genome

AF:

0.000519

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000893

Hom.:

Bravo

AF:

0.000691

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000675

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.1

DANN

Benign

0.74

DEOGEN2

Benign

0.056

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.11

Sift

Benign

0.64

.;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.068

MVP

0.16

MPC

0.35

ClinPred

0.012

GERP RS

-3.8

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over