Genetic Variant IL13:c.-220C>T (chr5-132657117-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001354992.2(IL13):c.-220C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 155,818 control chromosomes in the GnomAD database, including 5,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5693 hom., cov: 32)

Exomes 𝑓: 0.19 ( 61 hom. )

Consequence

IL13
NM_001354992.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.487

Publications

363 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
IL13	NM_001354992.2 link	c.-220C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 6	NP_001341921.1
IL13	NM_001354993.2 link	c.-149C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	NP_001341922.1
IL13	NM_001354992.2 link	c.-220C>T	5_prime_UTR_variant	Exon 2 of 6	NP_001341921.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
IL13	ENST00000468334.5 link	n.420C>T	non_coding_transcript_exon_variant	Exon 2 of 5	3
IL13	ENST00000487267.5 link	n.147C>T	non_coding_transcript_exon_variant	Exon 2 of 6	3
TH2LCRR	ENST00000435042.1 link	n.94+7062G>A	intron_variant	Intron 1 of 3	5
IL13	ENST00000459878.5 link	n.107+487C>T	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39202

AN:

151940

Hom.:

5672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.188

AC:

706

AN:

3760

Hom.:

Cov.:

AF XY:

0.187

AC XY:

376

AN XY:

2012

show subpopulations

African (AFR)

AF:

0.375

AC:

AN:

American (AMR)

AF:

0.179

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

AN:

East Asian (EAS)

AF:

0.174

AC:

AN:

460

South Asian (SAS)

AF:

0.300

AC:

AN:

European-Finnish (FIN)

AF:

0.181

AC:

AN:

370

Middle Eastern (MID)

AF:

0.154

AC:

AN:

European-Non Finnish (NFE)

AF:

0.183

AC:

445

AN:

2428

Other (OTH)

AF:

0.191

AC:

AN:

220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.258

AC:

39261

AN:

152058

Hom.:

5693

Cov.:

AF XY:

0.258

AC XY:

19149

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.394

AC:

16320

AN:

41440

American (AMR)

AF:

0.221

AC:

3382

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3466

East Asian (EAS)

AF:

0.170

AC:

877

AN:

5170

South Asian (SAS)

AF:

0.214

AC:

1030

AN:

4822

European-Finnish (FIN)

AF:

0.207

AC:

2188

AN:

10572

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13995

AN:

67982

Other (OTH)

AF:

0.231

AC:

487

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1422

2845

4267

5690

7112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.225

Hom.:

6169

Bravo

AF:

0.264

Asia WGS

AF:

0.203

AC:

708

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Inherited susceptibility to asthma

Other:1

May 15, 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

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.6

(source)

DANN

Benign

0.42

PhyloP100

-0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-132657117-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over