Variant 12-56339747-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016584.3(IL23A):c.318G>A(p.Ser106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,613,792 control chromosomes in the GnomAD database, including 3,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 222 hom., cov: 31)

Exomes 𝑓: 0.059 ( 2905 hom. )

Consequence

IL23A
NM_016584.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.248

Variant links:

Genes affected

IL23A (HGNC:15488): (interleukin 23 subunit alpha) This gene encodes a subunit of the heterodimeric cytokine interleukin 23 (IL23). IL23 is composed of this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the beta 1 subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). In contrast to IL12, which acts mainly on naive CD4(+) T cells, IL23 preferentially acts on memory CD4(+) T cells. [provided by RefSeq, Jul 2008]

IL23A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-56339747-G-A is Benign according to our data. Variant chr12-56339747-G-A is described in ClinVar as [Benign]. Clinvar id is 403490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.248 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL23A	NM_016584.3 linkuse as main transcript	c.318G>A	p.Ser106=	synonymous_variant	3/4	ENST00000228534.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IL23A	ENST00000228534.6 linkuse as main transcript	c.318G>A	p.Ser106=	synonymous_variant	3/4	1	NM_016584.3	P1
IL23A	ENST00000619177.1 linkuse as main transcript	n.263G>A		non_coding_transcript_exon_variant	4/5	2
IL23A	ENST00000622119.4 linkuse as main transcript	n.256G>A		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6931

AN:

152030

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.0495

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0536

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0683

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0486

AC:

12197

AN:

250870

Hom.:

365

AF XY:

0.0481

AC XY:

6530

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00908

Gnomad AMR exome

AF:

0.0530

Gnomad ASJ exome

AF:

0.0232

Gnomad EAS exome

AF:

0.0284

Gnomad SAS exome

AF:

0.0238

Gnomad FIN exome

AF:

0.0554

Gnomad NFE exome

AF:

0.0640

Gnomad OTH exome

AF:

0.0444

GnomAD4 exome

AF:

0.0592

AC:

86571

AN:

1461644

Hom.:

2905

Cov.:

AF XY:

0.0587

AC XY:

42708

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00818

Gnomad4 AMR exome

AF:

0.0526

Gnomad4 ASJ exome

AF:

0.0241

Gnomad4 EAS exome

AF:

0.0360

Gnomad4 SAS exome

AF:

0.0223

Gnomad4 FIN exome

AF:

0.0546

Gnomad4 NFE exome

AF:

0.0663

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0456

AC:

6943

AN:

152148

Hom.:

222

Cov.:

AF XY:

0.0447

AC XY:

3321

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0527

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.0339

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0536

Gnomad4 NFE

AF:

0.0683

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0560

Hom.:

353

Bravo

AF:

0.0421

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

EpiCase

AF:

0.0617

EpiControl

AF:

0.0570

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.9

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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