9-6222302-T-G

Variant names:

• chr9-6222302-T-G
• rs996029
• NM_033439.4:c.-12+6450T>G

Variant summary

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

The NM_033439.4(IL33):​c.-12+6450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,270 control chromosomes in the GnomAD database, including 67,715 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 0.94 (67715 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-12+6450T>G		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.-12+6450T>G		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-12+6450T>G		intron_variant	Intron 1 of 4	2		ENSP00000394039.2

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143405 AN: 152152 Hom.: 67659 Cov.: 32

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.943 AC: 143520 AN: 152270 Hom.: 67715 Cov.: 32 AF XY: 0.945 AC XY: 70358 AN XY: 74438

African (AFR) AF: 0.892 AC: 37049 AN: 41538

American (AMR) AF: 0.955 AC: 14604 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3335 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5182

South Asian (SAS) AF: 0.992 AC: 4787 AN: 4828

European-Finnish (FIN) AF: 0.981 AC: 10407 AN: 10608

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65023 AN: 68036

Other (OTH) AF: 0.938 AC: 1983 AN: 2114

Alfa AF: 0.952 Hom.: 107081

Bravo AF: 0.939

Asia WGS AF: 0.991 AC: 3443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		0.058
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: rs996029; hg19: chr9-6222302;