dbSNP rs10435816: IL33:c.-12+9683A>G (chr9-6225535-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033439.4(IL33):c.-12+9683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,858 control chromosomes in the GnomAD database, including 10,492 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 0.34 ( 10492 hom., cov: 31)

Consequence

IL33
NM_033439.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4 link	c.-12+9683A>G		intron_variant	Intron 1 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.-12+9683A>G		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1		O95760-1
IL33	ENST00000417746.6 link	c.-12+9683A>G		intron_variant	Intron 1 of 4	2		ENSP00000394039.2		O95760-4

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52092

AN:

151740

Hom.:

10455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.344

AC:

52169

AN:

151858

Hom.:

10492

Cov.:

AF XY:

0.338

AC XY:

25088

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.554

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.267

Hom.:

9560

Bravo

AF:

0.350

Asia WGS

AF:

0.421

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.3

DANN

Benign

0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over