chr12-56339010-G-T

Variant names:

• chr12-56339010-G-T
• rs11465744
• NM_016584.3:c.-35G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016584.3(IL23A):​c.-35G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000829 in 1,206,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: IL23A NM_016584.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.29e-7 AC: 1 AN: 1206160 Hom.: 0 Cov.: 30 AF XY: 0.00000172 AC XY: 1 AN XY: 581034

African (AFR) AF: 0.00 AC: 0 AN: 26704

American (AMR) AF: 0.00 AC: 0 AN: 20898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16266

East Asian (EAS) AF: 0.00 AC: 0 AN: 33130

South Asian (SAS) AF: 0.00 AC: 0 AN: 36014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 977494

Other (OTH) AF: 0.00 AC: 0 AN: 48464

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.64
PromoterAI		0.010	Neutral

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

Other links and lift over

dbSNP: rs11465744; hg19: chr12-56732794;