X-118741045-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001560.3(IL13RA1):c.117T>A(p.Ser39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,115,170 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S39S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., 23 hem., cov: 23)

Exomes 𝑓: 0.000049 ( 0 hom. 12 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039765388).

BS2

High Hemizygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13RA1	NM_001560.3 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/11	ENST00000371666.8
IL13RA1	XM_047442096.1 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/11	1	NM_001560.3	P1	P78552-1
IL13RA1	ENST00000371642.1 linkuse as main transcript	c.117T>A	p.Ser39Arg	missense_variant	2/6	1			P78552-2
IL13RA1	ENST00000652600.1 linkuse as main transcript	c.111T>A	p.Ser37Arg	missense_variant	3/12

Frequencies

GnomAD3 genomes

AF:

0.000438

AC:

AN:

111852

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

AN XY:

34014

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00466

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

GnomAD3 exomes

AF:

0.000285

AC:

AN:

178863

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

63571

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00171

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:

0.00

Gnomad OTH exome

AF:

0.00136

GnomAD4 exome

AF:

0.0000488

AC:

AN:

1003318

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

293468

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00138

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:

0.0000232

GnomAD4 genome

AF:

0.000438

AC:

AN:

111852

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

AN XY:

34014

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00466

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:

0.000510

ExAC

AF:

0.000173

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

Jan 27, 2022

The c.117T>A (p.S39R) alteration is located in exon 2 (coding exon 2) of the IL13RA1 gene. This alteration results from a T to A substitution at nucleotide position 117, causing the serine (S) at amino acid position 39 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Uncertain

0.070

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.040

T;T

MetaSVM

Uncertain

-0.060

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.69

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.4

N;N

REVEL

Pathogenic

0.69

Sift

Benign

0.060

T;T

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.91

P;.

Vest4

0.23

MutPred

0.61

Loss of glycosylation at T36 (P = 0.0455);Loss of glycosylation at T36 (P = 0.0455);

MVP

0.96

MPC

0.22

ClinPred

0.12

GERP RS

0.58

Varity_R

0.86

gMVP

0.37

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