chr5-132660272-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002188.3(IL13):c.431A>G(p.Gln144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,648 control chromosomes in the GnomAD database, including 502,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.77 ( 45613 hom., cov: 33)

Exomes 𝑓: 0.79 ( 456594 hom. )

Consequence

IL13
NM_002188.3 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:2

Conservation

PhyloP100: -2.73

Variant links:

Genes affected

IL13 (HGNC:5973): (interleukin 13) This gene encodes an immunoregulatory cytokine produced primarily by activated Th2 cells. This cytokine is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4. [provided by RefSeq, Jul 2008]

IL13 links:

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

TH2LCRR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.8788516E-7).

BP6

Variant 5-132660272-A-G is Benign according to our data. Variant chr5-132660272-A-G is described in ClinVar as [Benign, risk_factor]. Clinvar id is 14673.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13	NM_002188.3 link	c.431A>G	p.Gln144Arg	missense_variant	Exon 4 of 4	ENST00000304506.7	NP_002179.2	P35225
IL13	NM_001354991.2 link	c.236A>G	p.Gln79Arg	missense_variant	Exon 5 of 5		NP_001341920.1
IL13	NM_001354992.2 link	c.236A>G	p.Gln79Arg	missense_variant	Exon 6 of 6		NP_001341921.1
IL13	NM_001354993.2 link	c.236A>G	p.Gln79Arg	missense_variant	Exon 5 of 5		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7 link	c.431A>G	p.Gln144Arg	missense_variant	Exon 4 of 4	1	NM_002188.3	ENSP00000304915.3		P35225

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117104

AN:

152080

Hom.:

45591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.817

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.782

GnomAD2 exomes

AF:

0.721

AC:

180758

AN:

250830

AF XY:

0.730

show subpopulations

Gnomad AFR exome

AF:

0.816

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.776

Gnomad EAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.786

AC:

1149254

AN:

1461450

Hom.:

456594

Cov.:

AF XY:

0.785

AC XY:

570680

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.821

AC:

27477

AN:

33476

Gnomad4 AMR exome

AF:

0.497

AC:

22184

AN:

44672

Gnomad4 ASJ exome

AF:

0.778

AC:

20330

AN:

26132

Gnomad4 EAS exome

AF:

0.681

AC:

27036

AN:

39688

Gnomad4 SAS exome

AF:

0.709

AC:

61157

AN:

86236

Gnomad4 FIN exome

AF:

0.628

AC:

33408

AN:

53200

Gnomad4 NFE exome

AF:

0.815

AC:

905775

AN:

1111898

Gnomad4 Remaining exome

AF:

0.784

AC:

47349

AN:

60384

Heterozygous variant carriers

13063

26127

39190

52254

65317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20812

41624

62436

83248

104060

<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:

0.770

AC:

117176

AN:

152198

Hom.:

45613

Cov.:

AF XY:

0.759

AC XY:

56459

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.817

AC:

0.817066

AN:

0.817066

Gnomad4 AMR

AF:

0.670

AC:

0.669762

AN:

0.669762

Gnomad4 ASJ

AF:

0.768

AC:

0.767723

AN:

0.767723

Gnomad4 EAS

AF:

0.672

AC:

0.671941

AN:

0.671941

Gnomad4 SAS

AF:

0.710

AC:

0.710187

AN:

0.710187

Gnomad4 FIN

AF:

0.611

AC:

0.611279

AN:

0.611279

Gnomad4 NFE

AF:

0.798

AC:

0.798112

AN:

0.798112

Gnomad4 OTH

AF:

0.783

AC:

0.783144

AN:

0.783144

Heterozygous variant carriers

1347

2693

4040

5386

6733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.789

Hom.:

235883

Bravo

AF:

0.775

TwinsUK

AF:

0.815

AC:

3021

ALSPAC

AF:

0.820

AC:

3159

ESP6500AA

AF:

0.828

AC:

3647

ESP6500EA

AF:

0.805

AC:

6923

ExAC

AF:

0.733

AC:

88995

Asia WGS

AF:

0.690

AC:

2400

AN:

3478

EpiCase

AF:

0.811

EpiControl

AF:

0.817

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL13-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inherited susceptibility to asthma

Other:1

Mar 01, 2005

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Allergic rhinitis, susceptibility to

Other:1

Mar 01, 2005

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0020

DANN

Benign

0.18

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.18

T;.

MetaRNN

Benign

8.9e-7

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

0.020

.;N

REVEL

Benign

0.0080

Sift

Benign

1.0

.;T

Sift4G

Benign

0.58

T;T

Vest4

0.013

MPC

0.15

ClinPred

0.016

GERP RS

-7.2

gMVP

0.054

Mutation Taster

=99/1

polymorphism (auto)

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

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