rs16924144

Variant names:

• chr9-6221246-T-C
• rs16924144
• NM_033439.4:c.-12+5394T>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.-12+5394T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,102 control chromosomes in the GnomAD database, including 7,225 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 0.29 (7225 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-12+5394T>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.-12+5394T>C		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-12+5394T>C		intron_variant	Intron 1 of 4	2		ENSP00000394039.2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44299 AN: 151984 Hom.: 7219 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.291 AC: 44303 AN: 152102 Hom.: 7225 Cov.: 32 AF XY: 0.295 AC XY: 21911 AN XY: 74372

African (AFR) AF: 0.153 AC: 6359 AN: 41530

American (AMR) AF: 0.368 AC: 5612 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1638 AN: 5174

South Asian (SAS) AF: 0.375 AC: 1811 AN: 4826

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23291 AN: 67960

Other (OTH) AF: 0.315 AC: 664 AN: 2108

Alfa AF: 0.329 Hom.: 15743

Bravo AF: 0.289

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.87
PhyloP100		-1.4
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: rs16924144; hg19: chr9-6221246; COSMIC: COSV70307196;