rs10435816

Variant names:

• chr9-6225535-A-G
• rs10435816
• NM_033439.4:c.-12+9683A>G

Variant summary

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

The ENST00000682010.1(IL33):​c.-12+9683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,858 control chromosomes in the GnomAD database, including 10,492 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 0.34 (10492 hom., cov: 31)
• Consequence: IL33 ENST00000682010.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682010.1. 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.-12+9683A>G		intron	N/A	NP_254274.1
	IL33	NM_001314044.2		c.-12+10333A>G		intron	N/A	NP_001300973.1
	IL33	NM_001314046.2		c.-12+9683A>G		intron	N/A	NP_001300975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.-12+9683A>G		intron	N/A	ENSP00000507310.1
	IL33	ENST00000417746.6	TSL:2	c.-12+9683A>G		intron	N/A	ENSP00000394039.2
	ENSG00000294323	ENST00000722750.1		n.293-25T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52092 AN: 151740 Hom.: 10455 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.344 AC: 52169 AN: 151858 Hom.: 10492 Cov.: 31 AF XY: 0.338 AC XY: 25088 AN XY: 74202

African (AFR) AF: 0.554 AC: 22919 AN: 41376

American (AMR) AF: 0.234 AC: 3570 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2314 AN: 5166

South Asian (SAS) AF: 0.292 AC: 1401 AN: 4804

European-Finnish (FIN) AF: 0.257 AC: 2712 AN: 10536

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17316 AN: 67936

Other (OTH) AF: 0.296 AC: 624 AN: 2108

Alfa AF: 0.283 Hom.: 25697

Bravo AF: 0.350

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.40
PhyloP100		0.30
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: rs10435816; hg19: chr9-6225535; COSMIC: COSV70307719;