X-118727706-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/20 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.32

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21681115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13RA1	NM_001560.3 linkuse as main transcript	c.68G>A	p.Gly23Asp	missense_variant	1/11	ENST00000371666.8
IL13RA1	XM_047442096.1 linkuse as main transcript	c.68G>A	p.Gly23Asp	missense_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8 linkuse as main transcript	c.68G>A	p.Gly23Asp	missense_variant	1/11	1	NM_001560.3	P1	P78552-1
IL13RA1	ENST00000371642.1 linkuse as main transcript	c.68G>A	p.Gly23Asp	missense_variant	1/6	1			P78552-2
IL13RA1	ENST00000652600.1 linkuse as main transcript	c.-1+344G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33544

show subpopulations

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:

AN:

783603

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

231103

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33544

show subpopulations

Gnomad4 AFR

AF:

0.0000651

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Jan 10, 2023

The c.68G>A (p.G23D) alteration is located in exon 1 (coding exon 1) of the IL13RA1 gene. This alteration results from a G to A substitution at nucleotide position 68, causing the glycine (G) at amino acid position 23 to be replaced by an aspartic acid (D). 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

0.16

BayesDel_addAF

Benign

0.00085

BayesDel_noAF

Benign

-0.24

Cadd

Benign

3.3

Dann

Benign

0.90

DEOGEN2

Benign

0.12

T;.

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.35

T;T

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.070

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.15

T;T

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;.

Vest4

0.28

MutPred

0.25

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.91

MPC

0.76

ClinPred

0.19

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.058

gMVP

0.35

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