Genetic Variant NM_001560.3:c.838G>A (chrX-118766539-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/21 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001560.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA1	NM_001560.3	MANE Select	c.838G>A	p.Ala280Thr	missense	Exon 7 of 11	NP_001551.1	P78552-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL13RA1	ENST00000371666.8	TSL:1 MANE Select	c.838G>A	p.Ala280Thr	missense	Exon 7 of 11	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000965042.1		c.979G>A	p.Ala327Thr	missense	Exon 8 of 12	ENSP00000635101.1
IL13RA1	ENST00000865793.1		c.838G>A	p.Ala280Thr	missense	Exon 7 of 12	ENSP00000535852.1

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

African (AFR)

AF:

0.00

AC:

AN:

23085

American (AMR)

AF:

0.00

AC:

AN:

34676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18207

East Asian (EAS)

AF:

0.00

AC:

AN:

29320

South Asian (SAS)

AF:

0.00

AC:

AN:

49564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3746

European-Non Finnish (NFE)

AF:

0.00000147

AC:

AN:

679864

Other (OTH)

AF:

0.00

AC:

AN:

40070

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.8

(source)

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

PhyloP100

0.13

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

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over