9-6247430-C-T

Variant names:

• chr9-6247430-C-T
• rs7037276
• NM_033439.4:c.92-3044C>T

Variant summary

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

The NM_033439.4(IL33):​c.92-3044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,284 control chromosomes in the GnomAD database, including 67,685 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 0.94 (67685 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.92-3044C>T		intron_variant	Intron 2 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.92-3044C>T		intron_variant	Intron 2 of 7		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143439 AN: 152166 Hom.: 67624 Cov.: 31

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.943 AC: 143559 AN: 152284 Hom.: 67685 Cov.: 31 AF XY: 0.945 AC XY: 70351 AN XY: 74474

African (AFR) AF: 0.944 AC: 39227 AN: 41552

American (AMR) AF: 0.949 AC: 14507 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3295 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5165 AN: 5168

South Asian (SAS) AF: 0.978 AC: 4722 AN: 4830

European-Finnish (FIN) AF: 0.959 AC: 10189 AN: 10628

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63342 AN: 68024

Other (OTH) AF: 0.934 AC: 1973 AN: 2112

Alfa AF: 0.933 Hom.: 126550

Bravo AF: 0.942

Asia WGS AF: 0.986 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.38
PhyloP100		0.15
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: rs7037276; hg19: chr9-6247430;