dbSNP rs11171806: IL23A:p.Ser106Ser (chr12-56339747-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016584.3(IL23A):c.318G>A(p.Ser106Ser) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S106S) has been classified as Uncertain significance.

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

Publications

45 publications found

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

new If you want to explore the variant's impact on the transcript NM_016584.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23A	NM_016584.3	MANE Select	c.318G>A	p.Ser106Ser	synonymous	Exon 3 of 4	NP_057668.1	Q9NPF7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL23A	ENST00000228534.6	TSL:1 MANE Select	c.318G>A	p.Ser106Ser	synonymous	Exon 3 of 4	ENSP00000228534.4	Q9NPF7
IL23A	ENST00000619177.1	TSL:2	n.263G>A		non_coding_transcript_exon	Exon 4 of 5
IL23A	ENST00000622119.4	TSL:2	n.256G>A		non_coding_transcript_exon	Exon 4 of 5

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

GnomAD2 exomes

AF:

0.0486

AC:

12197

AN:

250870

AF XY:

0.0481

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 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

African (AFR)

AF:

0.00818

AC:

274

AN:

33480

American (AMR)

AF:

0.0526

AC:

2349

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

629

AN:

26130

East Asian (EAS)

AF:

0.0360

AC:

1430

AN:

39700

South Asian (SAS)

AF:

0.0223

AC:

1920

AN:

86240

European-Finnish (FIN)

AF:

0.0546

AC:

2915

AN:

53406

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0663

AC:

73730

AN:

1111836

Other (OTH)

AF:

0.0534

AC:

3225

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

4162

8324

12485

16647

20809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2674

5348

8022

10696

13370

<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:

0.0456

AC:

6943

AN:

152148

Hom.:

222

Cov.:

AF XY:

0.0447

AC XY:

3321

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0110

AC:

458

AN:

41528

American (AMR)

AF:

0.0527

AC:

805

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3462

East Asian (EAS)

AF:

0.0339

AC:

175

AN:

5168

South Asian (SAS)

AF:

0.0201

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0536

AC:

568

AN:

10596

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0683

AC:

4645

AN:

67984

Other (OTH)

AF:

0.0336

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

325

651

976

1302

1627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0546

Hom.:

420

Bravo

AF:

0.0421

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

EpiCase

AF:

0.0617

EpiControl

AF:

0.0570

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.9

(source)

DANN

Benign

0.59

PhyloP100

-0.25

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over