Genetic Variant IL23A:n.108-585A>C (chr12-56338841-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000619177.1(IL23A):n.108-585A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 385,098 control chromosomes in the GnomAD database, including 3 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 0.0039 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

IL23A
ENST00000619177.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.65

Publications

5 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23A	NM_016584.3 link	c.-204A>C		upstream_gene_variant		ENST00000228534.6	NP_057668.1	Q9NPF7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL23A	ENST00000619177.1 link	n.108-585A>C	intron_variant	Intron 2 of 4	2
IL23A	ENST00000622119.4 link	n.101-585A>C	intron_variant	Intron 2 of 4	2
IL23A	ENST00000228534.6 link	c.-204A>C	upstream_gene_variant		1	NM_016584.3	ENSP00000228534.4	Q9NPF7

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

596

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000455

AC:

106

AN:

232932

Hom.:

Cov.:

AF XY:

0.000399

AC XY:

AN XY:

117878

show subpopulations

African (AFR)

AF:

0.0125

AC:

AN:

6800

American (AMR)

AF:

0.000858

AC:

AN:

6990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8668

East Asian (EAS)

AF:

0.00

AC:

AN:

21250

South Asian (SAS)

AF:

0.00

AC:

AN:

2336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18394

Middle Eastern (MID)

AF:

0.000809

AC:

AN:

1236

European-Non Finnish (NFE)

AF:

0.0000197

AC:

AN:

151916

Other (OTH)

AF:

0.000717

AC:

AN:

15342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00392

AC:

597

AN:

152166

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0140

AC:

581

AN:

41486

American (AMR)

AF:

0.000786

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00605

Hom.:

Bravo

AF:

0.00437

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

2.7

PromoterAI

-0.011

Neutral

(source)

Splicing

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