Variant X-118749717-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.427A>G(p.Lys143Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,182,137 control chromosomes in the GnomAD database, including 1 homozygotes. There are 48 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00014 ( 1 hom. 46 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13RA1	NM_001560.3 link	c.427A>G	p.Lys143Glu	missense_variant	4/11	ENST00000371666.8	NP_001551.1	P78552-1
IL13RA1	XM_047442096.1 link	c.427A>G	p.Lys143Glu	missense_variant	4/11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL13RA1	ENST00000371666.8 link	c.427A>G	p.Lys143Glu	missense_variant	4/11	1	NM_001560.3	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000371642.1 link	c.427A>G	p.Lys143Glu	missense_variant	4/6	1		ENSP00000360705.1	P78552-2
IL13RA1	ENST00000652600.1 link	c.421A>G	p.Lys141Glu	missense_variant	5/12			ENSP00000498980.1	A0A494C1C4
IL13RA1	ENST00000481868.1 link	n.15A>G		non_coding_transcript_exon_variant	1/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000627

AC:

AN:

111585

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33747

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000545

AC:

AN:

183354

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67818

show subpopulations

Gnomad AFR exome

AF:

0.0000760

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:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

149

AN:

1070552

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

337910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000386

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:

0.000174

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000627

AC:

AN:

111585

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33747

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:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

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

Apr 26, 2023

The c.427A>G (p.K143E) alteration is located in exon 4 (coding exon 4) of the IL13RA1 gene. This alteration results from a A to G substitution at nucleotide position 427, causing the lysine (K) at amino acid position 143 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

T;.

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.50

Sift

Benign

0.37

T;T

Sift4G

Benign

0.061

T;D

Polyphen

0.69

P;.

Vest4

0.39

MVP

0.87

MPC

0.29

ClinPred

0.056

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.48

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