dbSNP rs762448978: IL13RA1:p.Asp155Asn (chrX-118749753-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001560.3(IL13RA1):c.463G>A(p.Asp155Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000947 in 1,161,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000067 ( 0 hom. 3 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA1	NM_001560.3 link	c.463G>A	p.Asp155Asn	missense_variant	Exon 4 of 11	ENST00000371666.8	NP_001551.1	P78552-1
IL13RA1	XM_047442096.1 link	c.463G>A	p.Asp155Asn	missense_variant	Exon 4 of 11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL13RA1	ENST00000371666.8 link	c.463G>A	p.Asp155Asn	missense_variant	Exon 4 of 11	1	NM_001560.3	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000371642.1 link	c.463G>A	p.Asp155Asn	missense_variant	Exon 4 of 6	1		ENSP00000360705.1	P78552-2
IL13RA1	ENST00000652600.1 link	c.457G>A	p.Asp153Asn	missense_variant	Exon 5 of 12			ENSP00000498980.1	A0A494C1C4
IL13RA1	ENST00000481868.1 link	n.51G>A		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0000360

AC:

AN:

110974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33214

show subpopulations

Gnomad AFR

AF:

0.0000983

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000962

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:

0.0000109

AC:

AN:

183206

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67694

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:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000666

AC:

AN:

1050932

Hom.:

Cov.:

AF XY:

0.00000927

AC XY:

AN XY:

323506

show subpopulations

Gnomad4 AFR exome

AF:

0.0000784

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000501

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000360

AC:

AN:

110974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33214

show subpopulations

Gnomad4 AFR

AF:

0.0000983

Gnomad4 AMR

AF:

0.0000962

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:

0.0000340

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

May 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.463G>A (p.D155N) alteration is located in exon 4 (coding exon 4) of the IL13RA1 gene. This alteration results from a G to A substitution at nucleotide position 463, causing the aspartic acid (D) at amino acid position 155 to be replaced by an asparagine (N). 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

0.091

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

D;.

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

D;D

M_CAP

Pathogenic

0.50

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.9

M;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.015

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.22

MVP

0.96

MPC

0.56

ClinPred

0.84

GERP RS

4.4

Varity_R

0.60

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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