rs16924161

Variant names:

• chr9-6230912-T-C
• rs16924161
• NM_033439.4:c.-11-10772T>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.-11-10772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,196 control chromosomes in the GnomAD database, including 1,977 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 0.14 (1977 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-11-10772T>C		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.-11-10772T>C		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-11-10772T>C		intron_variant	Intron 1 of 4	2		ENSP00000394039.2
ENSG00000294323	ENST00000722750.1	n.187-2617A>G		intron_variant	Intron 2 of 3
ENSG00000294323	ENST00000722751.1	n.232-2617A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21257 AN: 152074 Hom.: 1963 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.140 AC: 21276 AN: 152196 Hom.: 1977 Cov.: 32 AF XY: 0.141 AC XY: 10526 AN XY: 74396

African (AFR) AF: 0.0522 AC: 2169 AN: 41560

American (AMR) AF: 0.121 AC: 1848 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2166 AN: 5152

South Asian (SAS) AF: 0.172 AC: 827 AN: 4818

European-Finnish (FIN) AF: 0.195 AC: 2069 AN: 10590

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11264 AN: 67994

Other (OTH) AF: 0.119 AC: 251 AN: 2116

Alfa AF: 0.150 Hom.: 2867

Bravo AF: 0.131

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
DANN	Benign	0.74
PhyloP100		0.39
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: rs16924161; hg19: chr9-6230912;