Genetic Variant IL13RA1:p.Asn293Asp (chrX-118766844-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001560.3(IL13RA1):c.877A>G(p.Asn293Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

IL13RA1
NM_001560.3 missense, splice_region

Scores

Splicing: ADA: 0.000004546

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity I13R1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07315403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA1	NM_001560.3 link	c.877A>G	p.Asn293Asp	missense_variant, splice_region_variant	Exon 8 of 11	ENST00000371666.8	NP_001551.1	P78552-1
IL13RA1	XM_047442096.1 link	c.877A>G	p.Asn293Asp	missense_variant, splice_region_variant	Exon 8 of 11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL13RA1	ENST00000371666.8 link	c.877A>G	p.Asn293Asp	missense_variant, splice_region_variant	Exon 8 of 11	1	NM_001560.3	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000652600.1 link	c.871A>G	p.Asn291Asp	missense_variant, splice_region_variant	Exon 9 of 12			ENSP00000498980.1	A0A494C1C4
IL13RA1	ENST00000481868.1 link	n.570A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

916284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

261638

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.877A>G (p.N293D) alteration is located in exon 8 (coding exon 8) of the IL13RA1 gene. This alteration results from a A to G substitution at nucleotide position 877, causing the asparagine (N) at amino acid position 293 to be replaced by an aspartic acid (D). 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

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.50

M_CAP

Benign

0.042

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.71

MutationAssessor

Benign

-0.71

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.63

REVEL

Benign

0.22

Sift

Benign

0.73

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.075

MutPred

0.43

Gain of sheet (P = 0.0827);

MVP

0.37

MPC

0.20

ClinPred

0.014

GERP RS

2.7

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000045

dbscSNV1_RF

Benign

0.0040

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over