Genetic Variant IL33:c.520+108G>T (chr9-6253710-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033439.4(IL33):c.520+108G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 761,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00089 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL33	NM_033439.4	MANE Select	c.520+108G>T	intron	N/A	NP_254274.1
IL33	NM_001314044.2		c.520+108G>T	intron	N/A	NP_001300973.1
IL33	NM_001314045.2		c.520+108G>T	intron	N/A	NP_001300974.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL33	ENST00000682010.1	MANE Select	c.520+108G>T	intron	N/A	ENSP00000507310.1
IL33	ENST00000381434.7	TSL:1	c.520+108G>T	intron	N/A	ENSP00000370842.3
IL33	ENST00000611532.4	TSL:1	c.394+108G>T	intron	N/A	ENSP00000478858.1

Frequencies

GnomAD3 genomes

AF:

0.000895

AC:

136

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000128

AC:

AN:

609578

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

317162

show subpopulations

African (AFR)

AF:

0.00398

AC:

AN:

15562

American (AMR)

AF:

0.000355

AC:

AN:

22514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15846

East Asian (EAS)

AF:

0.00

AC:

AN:

32676

South Asian (SAS)

AF:

0.00

AC:

AN:

47162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3180

European-Non Finnish (NFE)

AF:

0.00000503

AC:

AN:

398010

Other (OTH)

AF:

0.000197

AC:

AN:

30520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000894

AC:

136

AN:

152068

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00318

AC:

132

AN:

41480

American (AMR)

AF:

0.000196

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.1

(source)

DANN

Benign

0.77

PhyloP100

-0.32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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