Variant X-118766539-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001560.3(IL13RA1):c.838G>A(p.Ala280Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 918,912 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000011 ( 0 hom. 1 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.134

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08649334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13RA1	NM_001560.3 link	c.838G>A	p.Ala280Thr	missense_variant	7/11	ENST00000371666.8	NP_001551.1	P78552-1
IL13RA1	XM_047442096.1 link	c.838G>A	p.Ala280Thr	missense_variant	7/11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL13RA1	ENST00000371666.8 link	c.838G>A	p.Ala280Thr	missense_variant	7/11	1	NM_001560.3	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000652600.1 link	c.832G>A	p.Ala278Thr	missense_variant	8/12			ENSP00000498980.1	A0A494C1C4
IL13RA1	ENST00000481868.1 link	n.531G>A		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000109

AC:

AN:

918912

Hom.:

Cov.:

AF XY:

0.00000371

AC XY:

AN XY:

269570

show subpopulations

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:

0.00000147

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.838G>A (p.A280T) 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 838, causing the alanine (A) at amino acid position 280 to be replaced by a threonine (T). 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

0.080

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.8

DANN

Benign

0.41

DEOGEN2

Benign

0.085

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.56

M_CAP

Benign

0.077

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.33

PROVEAN

Benign

0.40

REVEL

Benign

0.12

Sift

Benign

0.59

Sift4G

Benign

0.88

Polyphen

0.20

Vest4

0.035

MutPred

0.29

Gain of disorder (P = 0.064);

MVP

0.61

MPC

0.17

ClinPred

0.080

GERP RS

-2.5

Varity_R

0.11

gMVP

0.31

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

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