Genetic Variant NM_001354991.2:c.-93+286A>G (chr5-132656916-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001354991.2(IL13):c.-93+286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0936 in 152,512 control chromosomes in the GnomAD database, including 1,738 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 0.094 ( 1737 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1 hom. )

Consequence

IL13
NM_001354991.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.723

Publications

6 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
IL13	NM_001354991.2 link	c.-93+286A>G	intron_variant	Intron 1 of 4	NP_001341920.1
IL13	NM_001354992.2 link	c.-271-150A>G	intron_variant	Intron 1 of 5	NP_001341921.1
IL13	NM_001354993.2 link	c.-200-150A>G	intron_variant	Intron 1 of 4	NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
TH2LCRR	ENST00000435042.1 link	n.94+7263T>C	intron_variant	Intron 1 of 3	5
IL13	ENST00000459878.5 link	n.107+286A>G	intron_variant	Intron 1 of 4	3
IL13	ENST00000468334.5 link	n.369-150A>G	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0935

AC:

14216

AN:

152054

Hom.:

1733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0409

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0740

GnomAD4 exome

AF:

0.0353

AC:

AN:

340

Hom.:

AF XY:

0.0313

AC XY:

AN XY:

224

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0194

AC:

AN:

258

Other (OTH)

AF:

0.150

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0937

AC:

14261

AN:

152172

Hom.:

1737

Cov.:

AF XY:

0.0916

AC XY:

6815

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.283

AC:

11741

AN:

41476

American (AMR)

AF:

0.0453

AC:

693

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0397

AC:

138

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0412

AC:

198

AN:

4808

European-Finnish (FIN)

AF:

0.00697

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0183

AC:

1242

AN:

68010

Other (OTH)

AF:

0.0732

AC:

154

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

560

1120

1680

2240

2800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0359

Hom.:

593

Bravo

AF:

0.106

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.4

(source)

DANN

Benign

0.25

PhyloP100

-0.72

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over