9-6255881-T-G

Variant names:

• chr9-6255881-T-G
• rs1332290
• NM_033439.4:c.613-87T>G

Variant summary

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

The NM_033439.4(IL33):​c.613-87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,005,546 control chromosomes in the GnomAD database, including 184,274 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 0.52 (22548 hom., cov: 31)
  • Exomes 𝑓: 0.61 (161726 hom.)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.613-87T>G		intron_variant	Intron 7 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.613-87T>G		intron_variant	Intron 7 of 7		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79269 AN: 151742 Hom.: 22529 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.609 AC: 519796 AN: 853686 Hom.: 161726 AF XY: 0.610 AC XY: 271593 AN XY: 445120

African (AFR) AF: 0.292 AC: 6134 AN: 21024

American (AMR) AF: 0.382 AC: 14449 AN: 37856

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 13547 AN: 19928

East Asian (EAS) AF: 0.536 AC: 19657 AN: 36700

South Asian (SAS) AF: 0.574 AC: 38171 AN: 66492

European-Finnish (FIN) AF: 0.617 AC: 31131 AN: 50420

Middle Eastern (MID) AF: 0.512 AC: 2285 AN: 4466

European-Non Finnish (NFE) AF: 0.642 AC: 370517 AN: 576886

Other (OTH) AF: 0.599 AC: 23905 AN: 39914

GnomAD4 genome AF: 0.522 AC: 79293 AN: 151860 Hom.: 22548 Cov.: 31 AF XY: 0.521 AC XY: 38651 AN XY: 74208

African (AFR) AF: 0.302 AC: 12497 AN: 41418

American (AMR) AF: 0.458 AC: 6974 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2340 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2736 AN: 5168

South Asian (SAS) AF: 0.577 AC: 2778 AN: 4814

European-Finnish (FIN) AF: 0.637 AC: 6719 AN: 10542

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43308 AN: 67918

Other (OTH) AF: 0.534 AC: 1126 AN: 2108

Alfa AF: 0.595 Hom.: 35335

Bravo AF: 0.499

Asia WGS AF: 0.576 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.78
PhyloP100		-0.13
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: rs1332290; hg19: chr9-6255881; COSMIC: COSV67342902;