rs2371494

Variant names:

• chr12-56334216-G-A
• rs2371494
• ENST00000619177.1:n.9G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-56334216-G-A
• chr12-56334216-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000619177.1(IL23A):​n.9G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,160 control chromosomes in the GnomAD database, including 6,224 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 0.20 (6224 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL23A ENST00000619177.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 21 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]

PAN2 (HGNC:20074): (poly(A) specific ribonuclease subunit PAN2) This gene encodes a deadenylase that functions as the catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex. The encoded protein is a magnesium dependent 3' to 5' exoribonuclease that is involved in the degradation of cytoplasmic mRNAs. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

PAN2 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome-intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000619177.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAN2	NM_014871.6	MANE Select	c.-469C>T		upstream_gene	N/A	NP_055686.4
	PAN2	NM_001394699.1		c.-469C>T		upstream_gene	N/A	NP_001381628.1
	PAN2	NM_001166279.3		c.-469C>T		upstream_gene	N/A	NP_001159751.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL23A	ENST00000619177.1	TSL:2	n.9G>A		non_coding_transcript_exon	Exon 1 of 5
	IL23A	ENST00000622119.4	TSL:2	n.43G>A		non_coding_transcript_exon	Exon 1 of 5
	PAN2	ENST00000440411.8	TSL:1 MANE Select	c.-469C>T		upstream_gene	N/A	ENSP00000388231.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29780 AN: 152042 Hom.: 6192 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.196 AC: 29875 AN: 152160 Hom.: 6224 Cov.: 32 AF XY: 0.190 AC XY: 14124 AN XY: 74398

African (AFR) AF: 0.529 AC: 21915 AN: 41458

American (AMR) AF: 0.118 AC: 1803 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.0345 AC: 179 AN: 5182

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4832

European-Finnish (FIN) AF: 0.0537 AC: 570 AN: 10608

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4822 AN: 68006

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.0973 Hom.: 2235

Bravo AF: 0.214

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.3
DANN	Benign	0.86
PhyloP100		-0.065
PromoterAI		-0.029	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2371494; hg19: chr12-56728000;