rs1425845329

Variant names:

• chrX-118727706-G-A
• rs1425845329
• NM_001560.3:c.68G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001560.3(IL13RA1):​c.68G>A​(p.Gly23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 110,924 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.32
• Publications: 0 publications found

Genes affected

IL13RA1 (HGNC:5974): (interleukin 13 receptor subunit alpha 1) The protein encoded by this gene is a subunit of the interleukin 13 receptor. This subunit forms a receptor complex with IL4 receptor alpha, a subunit shared by IL13 and IL4 receptors. This subunit serves as a primary IL13-binding subunit of the IL13 receptor, and may also be a component of IL4 receptors. This protein has been shown to bind tyrosine kinase TYK2, and thus may mediate the signaling processes that lead to the activation of JAK1, STAT3 and STAT6 induced by IL13 and IL4. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21681115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001560.3. 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
	IL13RA1	NM_001560.3	MANE Select	c.68G>A	p.Gly23Asp	missense	Exon 1 of 11	NP_001551.1	P78552-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA1	ENST00000371666.8	TSL:1 MANE Select	c.68G>A	p.Gly23Asp	missense	Exon 1 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000371642.1	TSL:1	c.68G>A	p.Gly23Asp	missense	Exon 1 of 6	ENSP00000360705.1	P78552-2
	IL13RA1	ENST00000965042.1		c.68G>A	p.Gly23Asp	missense	Exon 1 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 110924 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 783603 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 231103

African (AFR) AF: 0.00 AC: 0 AN: 16779

American (AMR) AF: 0.00 AC: 0 AN: 5633

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9415

East Asian (EAS) AF: 0.00 AC: 0 AN: 18210

South Asian (SAS) AF: 0.00 AC: 0 AN: 13591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15707

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 671118

Other (OTH) AF: 0.00 AC: 0 AN: 31310

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 110924 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33544

African (AFR) AF: 0.0000651 AC: 2 AN: 30736

American (AMR) AF: 0.00 AC: 0 AN: 10714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2632

East Asian (EAS) AF: 0.00 AC: 0 AN: 3443

South Asian (SAS) AF: 0.00 AC: 0 AN: 2742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5883

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52381

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.00085	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	3.3
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.070	N
REVEL	Uncertain	0.39
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.28
MutPred		0.25		Gain of relative solvent accessibility (P = 0.09)
MVP		0.91
MPC		0.76
ClinPred		0.19	T
GERP RS		-2.3
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.058
gMVP		0.35
Mutation Taster		=94/6	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: rs1425845329; hg19: chrX-117861669;