rs1124053

Variant names:

• chr14-23375770-C-T
• rs1124053
• NM_172314.2:c.376C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23375770-C-T
• chr14-23375770-C-A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_172314.2(IL25):​c.376C>T​(p.Arg126Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,614,086 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (5 hom., cov: 33)
  • Exomes 𝑓: 0.010 (98 hom.)
• Consequence: IL25 NM_172314.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.869
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015012741).
• BP6: Variant 14-23375770-C-T is Benign according to our data. Variant chr14-23375770-C-T is described in ClinVar as Benign. ClinVar VariationId is 775101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172314.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL25	NM_172314.2	MANE Select	c.376C>T	p.Arg126Trp	missense	Exon 3 of 3	NP_758525.1	Q9H293-2
	IL25	NM_022789.4		c.424C>T	p.Arg142Trp	missense	Exon 2 of 2	NP_073626.1	Q9H293-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL25	ENST00000397242.3	TSL:1 MANE Select	c.376C>T	p.Arg126Trp	missense	Exon 3 of 3	ENSP00000380417.2	Q9H293-2
	IL25	ENST00000329715.2	TSL:1	c.424C>T	p.Arg142Trp	missense	Exon 2 of 2	ENSP00000328111.2	Q9H293-1

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 962 AN: 152082 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00644 AC: 1618 AN: 251366 AF XY: 0.00644

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00986

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.0104 AC: 15229 AN: 1461888 Hom.: 98 Cov.: 34 AF XY: 0.0101 AC XY: 7341 AN XY: 727246

African (AFR) AF: 0.00173 AC: 58 AN: 33480

American (AMR) AF: 0.00416 AC: 186 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 446 AN: 26136

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39700

South Asian (SAS) AF: 0.00278 AC: 240 AN: 86258

European-Finnish (FIN) AF: 0.00217 AC: 116 AN: 53418

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0122 AC: 13621 AN: 1112010

Other (OTH) AF: 0.00879 AC: 531 AN: 60394

GnomAD4 genome AF: 0.00632 AC: 962 AN: 152198 Hom.: 5 Cov.: 33 AF XY: 0.00552 AC XY: 411 AN XY: 74428

African (AFR) AF: 0.00219 AC: 91 AN: 41506

American (AMR) AF: 0.00399 AC: 61 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0106 AC: 720 AN: 67994

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.0432 Hom.: 2953

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0138 AC: 53

ExAC AF: 0.00592 AC: 719

EpiCase AF: 0.00981

EpiControl AF: 0.0101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.87
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MVP		0.77
MPC		0.48
ClinPred		0.055	T
GERP RS		3.6
Varity_R		0.64
gMVP		0.68
Mutation Taster		=96/4	polymorphism

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: rs1124053; hg19: chr14-23844979; COSMIC: COSV59304841; COSMIC: COSV59304841;