rs10435816

chr9-6225535-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(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 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.-12+9683A>G		intron_variant		ENST00000682010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.-12+9683A>G		intron_variant			NM_033439.4	P1
IL33	ENST00000417746.6	c.-12+9683A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.296

Alfa AF: 0.267 Hom.: 9560

Bravo AF: 0.350

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.3
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10435816; hg19: chr9-6225535; COSMIC: COSV70307719;