Genetic Variant IL13:c.*695T>C (chr5-132660977-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002188.3(IL13):c.*695T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,610 control chromosomes in the GnomAD database, including 47,641 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.79 ( 47526 hom., cov: 32)

Exomes 𝑓: 0.68 ( 115 hom. )

Consequence

IL13
NM_002188.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.408

Publications

47 publications found

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
IL13	NM_002188.3 link	c.*695T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2 link	c.*695T>C	3_prime_UTR_variant	Exon 5 of 5		NP_001341920.1
IL13	NM_001354992.2 link	c.*695T>C	3_prime_UTR_variant	Exon 6 of 6		NP_001341921.1
IL13	NM_001354993.2 link	c.*695T>C	3_prime_UTR_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.*695T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_002188.3	ENSP00000304915.3
TH2LCRR	ENST00000435042.1 link	n.94+3202A>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.785

AC:

119321

AN:

151994

Hom.:

47486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.874

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.789

GnomAD4 exome

AF:

0.681

AC:

339

AN:

498

Hom.:

115

Cov.:

AF XY:

0.677

AC XY:

203

AN XY:

300

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.840

AC:

AN:

106

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.630

AC:

233

AN:

370

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.857

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.785

AC:

119418

AN:

152112

Hom.:

47526

Cov.:

AF XY:

0.774

AC XY:

57545

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.873

AC:

36256

AN:

41538

American (AMR)

AF:

0.668

AC:

10200

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.748

AC:

2596

AN:

3470

East Asian (EAS)

AF:

0.675

AC:

3481

AN:

5160

South Asian (SAS)

AF:

0.710

AC:

3421

AN:

4818

European-Finnish (FIN)

AF:

0.616

AC:

6482

AN:

10528

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54278

AN:

67998

Other (OTH)

AF:

0.792

AC:

1674

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1256

2512

3768

5024

6280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.786

Hom.:

21012

Bravo

AF:

0.792

Asia WGS

AF:

0.696

AC:

2422

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

(source)

DANN

Benign

0.68

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over