Genetic Variant NM_033439.4:c.520+108G>C (chr9-6253710-G-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_033439.4(IL33):c.520+108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 758,366 control chromosomes in the GnomAD database, including 41,394 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 ( 9849 hom., cov: 32)

Exomes 𝑓: 0.31 ( 31545 hom. )

Consequence

IL33
NM_033439.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

12 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4 link	c.520+108G>C		intron_variant	Intron 6 of 7	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.520+108G>C		intron_variant	Intron 6 of 7		NM_033439.4	ENSP00000507310.1		O95760-1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53554

AN:

151868

Hom.:

9832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.314

AC:

190530

AN:

606380

Hom.:

31545

AF XY:

0.316

AC XY:

99618

AN XY:

315474

show subpopulations

African (AFR)

AF:

0.365

AC:

5650

AN:

15472

American (AMR)

AF:

0.508

AC:

11363

AN:

22380

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

3958

AN:

15774

East Asian (EAS)

AF:

0.458

AC:

14910

AN:

32540

South Asian (SAS)

AF:

0.366

AC:

17089

AN:

46696

European-Finnish (FIN)

AF:

0.350

AC:

15384

AN:

43940

Middle Eastern (MID)

AF:

0.385

AC:

1222

AN:

3170

European-Non Finnish (NFE)

AF:

0.281

AC:

111347

AN:

396046

Other (OTH)

AF:

0.316

AC:

9607

AN:

30362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5622

11245

16867

22490

28112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2082

4164

6246

8328

10410

<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:

0.353

AC:

53595

AN:

151986

Hom.:

9849

Cov.:

AF XY:

0.359

AC XY:

26652

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.375

AC:

15551

AN:

41454

American (AMR)

AF:

0.462

AC:

7045

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3470

East Asian (EAS)

AF:

0.471

AC:

2428

AN:

5158

South Asian (SAS)

AF:

0.402

AC:

1934

AN:

4816

European-Finnish (FIN)

AF:

0.343

AC:

3617

AN:

10560

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21021

AN:

67954

Other (OTH)

AF:

0.349

AC:

735

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1756

3513

5269

7026

8782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.202

Hom.:

434

Bravo

AF:

0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.7

(source)

DANN

Benign

0.79

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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