Variant X-118766536-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001560.3(IL13RA1):c.835G>A(p.Glu279Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,007,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 5 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09262547).

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.835G>A	p.Glu279Lys	missense_variant	7/11	ENST00000371666.8
IL13RA1	XM_047442096.1 linkuse as main transcript	c.835G>A	p.Glu279Lys	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8 linkuse as main transcript	c.835G>A	p.Glu279Lys	missense_variant	7/11	1	NM_001560.3	P1	P78552-1
IL13RA1	ENST00000652600.1 linkuse as main transcript	c.829G>A	p.Glu277Lys	missense_variant	8/12
IL13RA1	ENST00000481868.1 linkuse as main transcript	n.528G>A		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111732

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33898

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000830

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000787

AC:

AN:

177866

Hom.:

AF XY:

0.0000798

AC XY:

AN XY:

62684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000771

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000892

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

895469

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

259331

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000274

Gnomad4 SAS exome

AF:

0.0000205

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111732

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33898

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000954

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000830

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.000115

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

Sep 14, 2023

The c.835G>A (p.E279K) alteration is located in exon 7 (coding exon 7) of the IL13RA1 gene. This alteration results from a G to A substitution at nucleotide position 835, causing the glutamic acid (E) at amino acid position 279 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.13

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.80

M_CAP

Benign

0.047

MetaRNN

Benign

0.093

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.36

Sift

Benign

0.17

Sift4G

Benign

0.070

Polyphen

0.99

Vest4

0.25

MutPred

0.57

Gain of ubiquitination at E279 (P = 0.0128);

MVP

0.83

MPC

0.21

ClinPred

0.18

GERP RS

3.6

Varity_R

0.26

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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