dbSNP rs10975519: IL33:p.Tyr163Tyr (chr9-6253571-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_033439.4(IL33):c.489C>T(p.Tyr163Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,598,998 control chromosomes in the GnomAD database, including 88,587 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 0.35 ( 9932 hom., cov: 31)

Exomes 𝑓: 0.32 ( 78655 hom. )

Consequence

IL33
NM_033439.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.111

Publications

54 publications found

Variant links:

Genes affected

IL33 (HGNC:16028): (interleukin 33) The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

IL33 links:

ENSG00000294323 (HGNC:):

ENSG00000294323 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4 link	c.489C>T	p.Tyr163Tyr	synonymous_variant	Exon 6 of 8	ENST00000682010.1	NP_254274.1	O95760-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1 link	c.489C>T	p.Tyr163Tyr	synonymous_variant	Exon 6 of 8		NM_033439.4	ENSP00000507310.1		O95760-1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53754

AN:

151766

Hom.:

9915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.352

GnomAD2 exomes

AF:

0.380

AC:

94377

AN:

248652

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.582

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.322

AC:

465608

AN:

1447114

Hom.:

78655

Cov.:

AF XY:

0.323

AC XY:

232761

AN XY:

720006

show subpopulations

African (AFR)

AF:

0.387

AC:

12822

AN:

33110

American (AMR)

AF:

0.565

AC:

24716

AN:

43770

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6958

AN:

25914

East Asian (EAS)

AF:

0.463

AC:

18290

AN:

39494

South Asian (SAS)

AF:

0.393

AC:

33231

AN:

84562

European-Finnish (FIN)

AF:

0.356

AC:

18889

AN:

53026

Middle Eastern (MID)

AF:

0.386

AC:

2210

AN:

5722

European-Non Finnish (NFE)

AF:

0.299

AC:

329188

AN:

1101690

Other (OTH)

AF:

0.323

AC:

19304

AN:

59826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

13311

26622

39933

53244

66555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10958

21916

32874

43832

54790

<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:

0.354

AC:

53795

AN:

151884

Hom.:

9932

Cov.:

AF XY:

0.360

AC XY:

26742

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.381

AC:

15758

AN:

41408

American (AMR)

AF:

0.462

AC:

7048

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3470

East Asian (EAS)

AF:

0.472

AC:

2434

AN:

5154

South Asian (SAS)

AF:

0.401

AC:

1925

AN:

4800

European-Finnish (FIN)

AF:

0.342

AC:

3602

AN:

10544

Middle Eastern (MID)

AF:

0.425

AC:

124

AN:

292

European-Non Finnish (NFE)

AF:

0.310

AC:

21026

AN:

67934

Other (OTH)

AF:

0.349

AC:

737

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1731

3462

5192

6923

8654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.334

Hom.:

16639

Bravo

AF:

0.365

Asia WGS

AF:

0.400

AC:

1388

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.49

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over