rs1330383

Variant names:

• chr9-6251507-G-T
• rs1330383
• NM_033439.4:c.343+242G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.343+242G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,854 control chromosomes in the GnomAD database, including 9,786 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 (9786 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 11 publications found

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]

ENSG00000294323 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.343+242G>T		intron_variant	Intron 4 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.343+242G>T		intron_variant	Intron 4 of 7		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53366 AN: 151736 Hom.: 9770 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.352 AC: 53404 AN: 151854 Hom.: 9786 Cov.: 31 AF XY: 0.358 AC XY: 26589 AN XY: 74206

African (AFR) AF: 0.370 AC: 15310 AN: 41384

American (AMR) AF: 0.460 AC: 7017 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2572 AN: 5170

South Asian (SAS) AF: 0.401 AC: 1923 AN: 4796

European-Finnish (FIN) AF: 0.342 AC: 3604 AN: 10538

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20983 AN: 67924

Other (OTH) AF: 0.348 AC: 732 AN: 2106

Alfa AF: 0.325 Hom.: 23841

Bravo AF: 0.362

Asia WGS AF: 0.402 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1330383; hg19: chr9-6251507; COSMIC: COSV67343561;