Variant X-118776495-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001560.3(IL13RA1):c.1175A>G(p.Gln392Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 832,134 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.000011 ( 0 hom. 0 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

Variant links:

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]

IL13RA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13RA1	NM_001560.3 linkuse as main transcript	c.1175A>G	p.Gln392Arg	missense_variant	10/11	ENST00000371666.8
IL13RA1	XM_047442096.1 linkuse as main transcript	c.1175A>G	p.Gln392Arg	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8 linkuse as main transcript	c.1175A>G	p.Gln392Arg	missense_variant	10/11	1	NM_001560.3	P1	P78552-1
IL13RA1	ENST00000652600.1 linkuse as main transcript	c.1169A>G	p.Gln390Arg	missense_variant	11/12

Frequencies

GnomAD3 genomes

AF:

0.0000556

AC:

AN:

107863

Hom.:

Cov.:

AF XY:

0.0000654

AC XY:

AN XY:

30601

show subpopulations

Gnomad AFR

AF:

0.0000337

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:

0.0000192

Gnomad OTH

AF:

0.00277

GnomAD3 exomes

AF:

0.0000226

AC:

AN:

176749

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61791

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000761

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000110

AC:

AN:

724271

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

200873

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000583

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000596

Gnomad4 OTH exome

AF:

0.0000896

GnomAD4 genome

AF:

0.0000556

AC:

AN:

107863

Hom.:

Cov.:

AF XY:

0.0000654

AC XY:

AN XY:

30601

show subpopulations

Gnomad4 AFR

AF:

0.0000337

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000192

Gnomad4 OTH

AF:

0.00277

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.1175A>G (p.Q392R) alteration is located in exon 10 (coding exon 10) of the IL13RA1 gene. This alteration results from a A to G substitution at nucleotide position 1175, causing the glutamine (Q) at amino acid position 392 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Uncertain

0.030

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.33

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.69

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.73

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.45

MutPred

0.51

Loss of sheet (P = 0.0228);

MVP

0.98

MPC

0.63

ClinPred

0.65

GERP RS

5.4

Varity_R

0.36

gMVP

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over