Variant 5-132660197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002188.3(IL13):c.356G>A(p.Arg119Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,614,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

IL13
NM_002188.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.255

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:

IL13 (HGNC:):

IL13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073035657).

BP6

Variant 5-132660197-G-A is Benign according to our data. Variant chr5-132660197-G-A is described in ClinVar as [Benign]. Clinvar id is 3045158.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_002188.3 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/4	ENST00000304506.7	NP_002179.2	P35225
IL13	NM_001354991.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	5/5		NP_001341920.1
IL13	NM_001354992.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	6/6		NP_001341921.1
IL13	NM_001354993.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	5/5		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7 linkuse as main transcript	c.356G>A	p.Arg119Gln	missense_variant	4/4	1	NM_002188.3	ENSP00000304915.3		P35225

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000525

AC:

132

AN:

251396

Hom.:

AF XY:

0.000419

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00578

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

189

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00541

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152298

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000395

Hom.:

Bravo

AF:

0.00222

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL13-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

DANN

Uncertain

0.98

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.73

T;.

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.048

Sift

Benign

0.11

.;T

Sift4G

Benign

0.38

T;T

Vest4

0.086

MVP

0.37

MPC

0.18

ClinPred

0.0069

GERP RS

-2.4

gMVP

0.065

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