Variant X-118758225-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001560.3(IL13RA1):c.659T>C(p.Val220Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000477 in 1,047,248 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000032 ( 0 hom. 1 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13RA1	NM_001560.3 linkuse as main transcript	c.659T>C	p.Val220Ala	missense_variant	5/11	ENST00000371666.8
IL13RA1	XM_047442096.1 linkuse as main transcript	c.659T>C	p.Val220Ala	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8 linkuse as main transcript	c.659T>C	p.Val220Ala	missense_variant	5/11	1	NM_001560.3	P1	P78552-1
IL13RA1	ENST00000371642.1 linkuse as main transcript	c.659T>C	p.Val220Ala	missense_variant	5/6	1			P78552-2
IL13RA1	ENST00000652600.1 linkuse as main transcript	c.653T>C	p.Val218Ala	missense_variant	6/12
IL13RA1	ENST00000481868.1 linkuse as main transcript	n.247T>C		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34162

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000116

AC:

AN:

173153

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

59377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000321

AC:

AN:

935264

Hom.:

Cov.:

AF XY:

0.00000399

AC XY:

AN XY:

250854

show subpopulations

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:

0.00000424

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34162

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Nov 09, 2023

The c.659T>C (p.V220A) alteration is located in exon 5 (coding exon 5) of the IL13RA1 gene. This alteration results from a T to C substitution at nucleotide position 659, causing the valine (V) at amino acid position 220 to be replaced by an alanine (A). 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

0.31

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;.

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.68

T;T

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

0.40

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.46

Sift

Benign

0.052

T;T

Sift4G

Uncertain

0.010

D;D

Polyphen

0.98

D;.

Vest4

0.53

MutPred

0.49

Loss of stability (P = 0.0577);Loss of stability (P = 0.0577);

MVP

0.89

MPC

0.60

ClinPred

0.67

GERP RS

5.6

Varity_R

0.41

gMVP

0.65

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