Genetic Variant IL13RA1:p.Arg225Ser (chrX-118758239-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001560.3(IL13RA1):c.673C>A(p.Arg225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 998,145 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 13 hem., cov: 21)

Exomes 𝑓: 0.000035 ( 0 hom. 7 hem. )

Consequence

IL13RA1
NM_001560.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.495

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024927706).

BS2

High Hemizygotes in GnomAd4 at 13 gene

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.673C>A	p.Arg225Ser	missense	Exon 5 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.673C>A	p.Arg225Ser	missense	Exon 5 of 11	ENSP00000360730.3	P78552-1
IL13RA1	ENST00000371642.1	TSL:1	c.673C>A	p.Arg225Ser	missense	Exon 5 of 6	ENSP00000360705.1	P78552-2
IL13RA1	ENST00000965042.1		c.814C>A	p.Arg272Ser	missense	Exon 6 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

111583

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000667

GnomAD2 exomes

AF:

0.000160

AC:

AN:

168749

AF XY:

0.000125

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000350

AC:

AN:

886562

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

229768

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

22582

American (AMR)

AF:

0.00

AC:

AN:

32376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16514

East Asian (EAS)

AF:

0.00

AC:

AN:

28808

South Asian (SAS)

AF:

0.00

AC:

AN:

40571

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37899

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3493

European-Non Finnish (NFE)

AF:

0.00000150

AC:

AN:

666490

Other (OTH)

AF:

0.0000529

AC:

AN:

37829

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000403

AC:

AN:

111583

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

AN XY:

33815

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

30657

American (AMR)

AF:

0.00

AC:

AN:

10501

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6047

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53071

Other (OTH)

AF:

0.000667

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

ClinVar

ClinVar submissions

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

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.025

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.4

PhyloP100

-0.49

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.090

REVEL

Benign

0.16

Sift

Benign

0.39

Sift4G

Benign

0.33

Polyphen

0.26

Vest4

0.31

MVP

0.70

MPC

0.29

ClinPred

0.014

GERP RS

0.30

Varity_R

0.29

gMVP

0.61

Mutation Taster

=99/1

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over