rs1124053

chr14-23375770-C-Achr14-23375770-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022789.4(IL25):c.424C>A(p.Arg142=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,614,028 control chromosomes in the GnomAD database, including 41,201 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 0.25 (5461 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35740 hom.)
• Consequence: IL25 NM_022789.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

Genes affected

IL25 (HGNC:13765): (interleukin 25) The protein encoded by this gene is a cytokine that shares sequence similarity with interleukin 17. This cytokine can induce NF-kappaB activation, and stimulate the production of interleukin 8. Both this cytokine and interleukin 17B are ligands for the cytokine receptor IL17BR. Studies of a similar gene in mice suggest that this cytokine may be a pro-inflammatory cytokine favoring the Th2-type immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=0.869 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL25	NM_172314.2	c.376C>A	p.Arg126=	synonymous_variant	3/3	ENST00000397242.3
IL25	NM_022789.4	c.424C>A	p.Arg142=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL25	ENST00000397242.3	c.376C>A	p.Arg126=	synonymous_variant	3/3	1	NM_172314.2	P2
IL25	ENST00000329715.2	c.424C>A	p.Arg142=	synonymous_variant	2/2	1		A2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38555 AN: 152038 Hom.: 5444 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.210 AC: 52860 AN: 251366 Hom.: 6045 AF XY: 0.209 AC XY: 28460 AN XY: 135878

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.217 AC: 317570 AN: 1461874 Hom.: 35740 Cov.: 34 AF XY: 0.216 AC XY: 156888 AN XY: 727234

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.254 AC: 38607 AN: 152154 Hom.: 5461 Cov.: 33 AF XY: 0.250 AC XY: 18602 AN XY: 74404

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.273

Alfa AF: 0.177 Hom.: 809

Bravo AF: 0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	9.6
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs1124053; hg19: chr14-23844979; COSMIC: COSV59305175; COSMIC: COSV59305175;