dbSNP rs2069744: IL13:c.175-441C>T (chr5-132658977-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_002188.3(IL13):c.175-441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 202,282 control chromosomes in the GnomAD database, including 1,884 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 0.091 ( 1743 hom., cov: 32)

Exomes 𝑓: 0.031 ( 141 hom. )

Consequence

IL13
NM_002188.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.176

Publications

21 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002188.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL13	NM_002188.3	MANE Select	c.175-441C>T	intron	N/A	NP_002179.2
IL13	NM_001354991.2		c.-21-441C>T	intron	N/A	NP_001341920.1	Q4VB53
IL13	NM_001354992.2		c.-21-441C>T	intron	N/A	NP_001341921.1	Q4VB53

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL13	ENST00000304506.7	TSL:1 MANE Select	c.175-441C>T	intron	N/A	ENSP00000304915.3	P35225
IL13	ENST00000462480.1	TSL:1	n.805C>T	non_coding_transcript_exon	Exon 1 of 3
TH2LCRR	ENST00000435042.1	TSL:5	n.94+5202G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13859

AN:

152050

Hom.:

1728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.0931

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.0732

GnomAD4 exome

AF:

0.0305

AC:

1529

AN:

50114

Hom.:

141

Cov.:

AF XY:

0.0283

AC XY:

728

AN XY:

25764

show subpopulations

African (AFR)

AF:

0.277

AC:

671

AN:

2426

American (AMR)

AF:

0.0665

AC:

284

AN:

4268

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

AN:

1194

East Asian (EAS)

AF:

0.0860

AC:

336

AN:

3906

South Asian (SAS)

AF:

0.00542

AC:

AN:

4984

European-Finnish (FIN)

AF:

0.0170

AC:

AN:

1410

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.00321

AC:

AN:

29258

Other (OTH)

AF:

0.0247

AC:

AN:

2510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

133

199

266

332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.0915

AC:

13917

AN:

152168

Hom.:

1743

Cov.:

AF XY:

0.0898

AC XY:

6682

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.280

AC:

11636

AN:

41484

American (AMR)

AF:

0.0680

AC:

1040

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0931

AC:

481

AN:

5166

South Asian (SAS)

AF:

0.0118

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0208

AC:

221

AN:

10608

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00366

AC:

249

AN:

68012

Other (OTH)

AF:

0.0724

AC:

153

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

539

1078

1616

2155

2694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0617

Hom.:

183

Bravo

AF:

0.105

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.53

PhyloP100

0.18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over