dbSNP rs12000491: IL33:c.*1199T>C (chr9-6257367-T-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.*1199T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,612 control chromosomes in the GnomAD database, including 980 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 0.078 ( 980 hom., cov: 32)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

IL33
NM_033439.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 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	UniProt
IL33	NM_033439.4	MANE Select	c.*1199T>C	3_prime_UTR	Exon 8 of 8	NP_254274.1	O95760-1
IL33	NM_001314044.2		c.*1199T>C	3_prime_UTR	Exon 8 of 8	NP_001300973.1	O95760-1
IL33	NM_001314045.2		c.*1199T>C	3_prime_UTR	Exon 8 of 8	NP_001300974.1	O95760-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL33	ENST00000682010.1	MANE Select	c.*1199T>C	3_prime_UTR	Exon 8 of 8	ENSP00000507310.1	O95760-1
IL33	ENST00000381434.7	TSL:1	c.*1199T>C	3_prime_UTR	Exon 7 of 7	ENSP00000370842.3	O95760-1
IL33	ENST00000893939.1		c.*1199T>C	3_prime_UTR	Exon 8 of 8	ENSP00000563998.1

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11784

AN:

152134

Hom.:

971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0384

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0651

GnomAD4 exome

AF:

0.0417

AC:

AN:

360

Hom.:

Cov.:

AF XY:

0.0348

AC XY:

AN XY:

230

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0429

AC:

AN:

350

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

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:

0.0777

AC:

11826

AN:

152252

Hom.:

980

Cov.:

AF XY:

0.0749

AC XY:

5575

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.206

AC:

8551

AN:

41498

American (AMR)

AF:

0.0383

AC:

586

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0151

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0322

AC:

342

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0285

AC:

1940

AN:

68026

Other (OTH)

AF:

0.0644

AC:

136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

501

1002

1504

2005

2506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0488

Hom.:

535

Bravo

AF:

0.0834

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

0.0

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