9-6240658-T-C

Variant names:

• chr9-6240658-T-C
• rs10118795
• NM_033439.4:c.-11-1026T>C

Variant summary

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

The NM_033439.4(IL33):​c.-11-1026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,000 control chromosomes in the GnomAD database, including 30,679 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 (30679 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	NM_033439.4	MANE Select	c.-11-1026T>C		intron	N/A	NP_254274.1
	IL33	NM_001314044.2		c.-11-1026T>C		intron	N/A	NP_001300973.1
	IL33	NM_001314045.2		c.-11-1026T>C		intron	N/A	NP_001300974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.-11-1026T>C		intron	N/A	ENSP00000507310.1
	IL33	ENST00000417746.6	TSL:2	c.-11-1026T>C		intron	N/A	ENSP00000394039.2
	ENSG00000294323	ENST00000722750.1		n.187-12363A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94753 AN: 151882 Hom.: 30668 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.624 AC: 94788 AN: 152000 Hom.: 30679 Cov.: 31 AF XY: 0.630 AC XY: 46823 AN XY: 74296

African (AFR) AF: 0.444 AC: 18410 AN: 41444

American (AMR) AF: 0.730 AC: 11154 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2726 AN: 5158

South Asian (SAS) AF: 0.679 AC: 3266 AN: 4812

European-Finnish (FIN) AF: 0.724 AC: 7639 AN: 10548

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47077 AN: 67980

Other (OTH) AF: 0.656 AC: 1386 AN: 2112

Alfa AF: 0.657 Hom.: 13110

Bravo AF: 0.617

Asia WGS AF: 0.553 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		-1.7
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: rs10118795; hg19: chr9-6240658;