chr9-6255319-G-A

Variant names:

• chr9-6255319-G-A
• rs7047921
• NM_033439.4:c.613-649G>A

Variant summary

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

The NM_033439.4(IL33):​c.613-649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,880 control chromosomes in the GnomAD database, including 9,935 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 (9935 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.613-649G>A		intron_variant	Intron 7 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.613-649G>A		intron_variant	Intron 7 of 7		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53800 AN: 151762 Hom.: 9919 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.354 AC: 53839 AN: 151880 Hom.: 9935 Cov.: 31 AF XY: 0.360 AC XY: 26754 AN XY: 74236

African (AFR) AF: 0.382 AC: 15841 AN: 41428

American (AMR) AF: 0.462 AC: 7036 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2422 AN: 5158

South Asian (SAS) AF: 0.399 AC: 1927 AN: 4824

European-Finnish (FIN) AF: 0.342 AC: 3596 AN: 10518

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20992 AN: 67930

Other (OTH) AF: 0.348 AC: 733 AN: 2108

Alfa AF: 0.358 Hom.: 1778

Bravo AF: 0.365

Asia WGS AF: 0.392 AC: 1359 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.44
PhyloP100		1.6
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: rs7047921; hg19: chr9-6255319; COSMIC: COSV67343586;