9-6233279-A-T

Variant names:

• chr9-6233279-A-T
• rs16924171
• NM_033439.4:c.-11-8405A>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.-11-8405A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,016 control chromosomes in the GnomAD database, including 30,549 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 0.62 (30549 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-11-8405A>T		intron_variant	Intron 1 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.-11-8405A>T		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-11-8405A>T		intron_variant	Intron 1 of 4	2		ENSP00000394039.2
ENSG00000294323	ENST00000722750.1	n.187-4984T>A		intron_variant	Intron 2 of 3
ENSG00000294323	ENST00000722751.1	n.232-4984T>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94497 AN: 151898 Hom.: 30538 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.622 AC: 94536 AN: 152016 Hom.: 30549 Cov.: 32 AF XY: 0.628 AC XY: 46681 AN XY: 74322

African (AFR) AF: 0.439 AC: 18202 AN: 41420

American (AMR) AF: 0.729 AC: 11140 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2272 AN: 3466

East Asian (EAS) AF: 0.520 AC: 2687 AN: 5168

South Asian (SAS) AF: 0.677 AC: 3267 AN: 4826

European-Finnish (FIN) AF: 0.722 AC: 7633 AN: 10568

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47036 AN: 67982

Other (OTH) AF: 0.656 AC: 1383 AN: 2108

Alfa AF: 0.558 Hom.: 1758

Bravo AF: 0.616

Asia WGS AF: 0.549 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16924171; hg19: chr9-6233279;