Genetic Variant IL23A:c.-35G>A (chr12-56339010-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_016584.3(IL23A):c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,358,458 control chromosomes in the GnomAD database, including 35 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 0.0083 ( 22 hom., cov: 31)

Exomes 𝑓: 0.00085 ( 13 hom. )

Consequence

IL23A
NM_016584.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.639

Publications

1 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:

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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=-0.86).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00835 (1271/152306) while in subpopulation AFR AF = 0.029 (1204/41556). AF 95% confidence interval is 0.0276. There are 22 homozygotes in GnomAd4. There are 625 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23A	NM_016584.3 link	c.-35G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000228534.6	NP_057668.1	Q9NPF7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL23A	ENST00000228534.6 link	c.-35G>A	5_prime_UTR_variant	Exon 1 of 4	1	NM_016584.3	ENSP00000228534.4	Q9NPF7
IL23A	ENST00000619177.1 link	n.108-416G>A	intron_variant	Intron 2 of 4	2
IL23A	ENST00000622119.4 link	n.101-416G>A	intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1273

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

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:

0.000162

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00259

AC:

365

AN:

140962

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.0280

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00144

GnomAD4 exome

AF:

0.000846

AC:

1021

AN:

1206152

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

465

AN XY:

581032

show subpopulations

African (AFR)

AF:

0.0302

AC:

807

AN:

26700

American (AMR)

AF:

0.00110

AC:

AN:

20898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16266

East Asian (EAS)

AF:

0.00

AC:

AN:

33130

South Asian (SAS)

AF:

0.0000555

AC:

AN:

36014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42444

Middle Eastern (MID)

AF:

0.000421

AC:

AN:

4746

European-Non Finnish (NFE)

AF:

0.000122

AC:

119

AN:

977492

Other (OTH)

AF:

0.00140

AC:

AN:

48462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

131

174

218

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:

0.00835

AC:

1271

AN:

152306

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

625

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0290

AC:

1204

AN:

41556

American (AMR)

AF:

0.00287

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68024

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00522

Hom.:

Bravo

AF:

0.00944

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

(source)

DANN

Benign

0.75

PhyloP100

-0.64

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=298/2

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

Computational scores

Splicing

Publications

Other links and lift over