Genetic Variant NM_033439.4:c.613-87T>G (chr9-6255881-T-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_033439.4(IL33):c.613-87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,005,546 control chromosomes in the GnomAD database, including 184,274 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 0.52 ( 22548 hom., cov: 31)

Exomes 𝑓: 0.61 ( 161726 hom. )

Consequence

IL33
NM_033439.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126

Publications

15 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

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.613-87T>G	intron	N/A	NP_254274.1
IL33	NM_001314044.2		c.613-87T>G	intron	N/A	NP_001300973.1
IL33	NM_001314045.2		c.613-87T>G	intron	N/A	NP_001300974.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IL33	ENST00000682010.1	MANE Select	c.613-87T>G	intron	N/A	ENSP00000507310.1
IL33	ENST00000381434.7	TSL:1	c.613-87T>G	intron	N/A	ENSP00000370842.3
IL33	ENST00000611532.4	TSL:1	c.487-87T>G	intron	N/A	ENSP00000478858.1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79269

AN:

151742

Hom.:

22529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.741

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.637

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.638

Gnomad OTH

AF:

0.530

GnomAD4 exome

AF:

0.609

AC:

519796

AN:

853686

Hom.:

161726

AF XY:

0.610

AC XY:

271593

AN XY:

445120

show subpopulations

African (AFR)

AF:

0.292

AC:

6134

AN:

21024

American (AMR)

AF:

0.382

AC:

14449

AN:

37856

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

13547

AN:

19928

East Asian (EAS)

AF:

0.536

AC:

19657

AN:

36700

South Asian (SAS)

AF:

0.574

AC:

38171

AN:

66492

European-Finnish (FIN)

AF:

0.617

AC:

31131

AN:

50420

Middle Eastern (MID)

AF:

0.512

AC:

2285

AN:

4466

European-Non Finnish (NFE)

AF:

0.642

AC:

370517

AN:

576886

Other (OTH)

AF:

0.599

AC:

23905

AN:

39914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

9883

19766

29649

39532

49415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6702

13404

20106

26808

33510

<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:

0.522

AC:

79293

AN:

151860

Hom.:

22548

Cov.:

AF XY:

0.521

AC XY:

38651

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.302

AC:

12497

AN:

41418

American (AMR)

AF:

0.458

AC:

6974

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

2340

AN:

3470

East Asian (EAS)

AF:

0.529

AC:

2736

AN:

5168

South Asian (SAS)

AF:

0.577

AC:

2778

AN:

4814

European-Finnish (FIN)

AF:

0.637

AC:

6719

AN:

10542

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.638

AC:

43308

AN:

67918

Other (OTH)

AF:

0.534

AC:

1126

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1784

3567

5351

7134

8918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.595

Hom.:

35335

Bravo

AF:

0.499

Asia WGS

AF:

0.576

AC:

2002

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

(source)

DANN

Benign

0.78

PhyloP100

-0.13

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