chr9-6251588-T-C

Variant names:

• chr9-6251588-T-C
• rs1929992
• NM_033439.4:c.343+323T>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.343+323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,932 control chromosomes in the GnomAD database, including 10,067 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 0.36 (10067 hom., cov: 30)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 41 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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.343+323T>C		intron	N/A	NP_254274.1
	IL33	NM_001314044.2		c.343+323T>C		intron	N/A	NP_001300973.1
	IL33	NM_001314045.2		c.343+323T>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.343+323T>C		intron	N/A	ENSP00000507310.1
	IL33	ENST00000381434.7	TSL:1	c.343+323T>C		intron	N/A	ENSP00000370842.3
	IL33	ENST00000611532.4	TSL:1	c.217+989T>C		intron	N/A	ENSP00000478858.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54072 AN: 151814 Hom.: 10048 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.356 AC: 54114 AN: 151932 Hom.: 10067 Cov.: 30 AF XY: 0.363 AC XY: 26914 AN XY: 74238

African (AFR) AF: 0.385 AC: 15946 AN: 41440

American (AMR) AF: 0.462 AC: 7046 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3462

East Asian (EAS) AF: 0.500 AC: 2577 AN: 5158

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4804

European-Finnish (FIN) AF: 0.341 AC: 3589 AN: 10538

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21006 AN: 67956

Other (OTH) AF: 0.351 AC: 741 AN: 2114

Alfa AF: 0.344 Hom.: 1163

Bravo AF: 0.367

Asia WGS AF: 0.404 AC: 1404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.88
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1929992; hg19: chr9-6251588; COSMIC: COSV67343563;