9-6248035-C-T

Position:

• chr9-6248035-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.92-2439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,732 control chromosomes in the GnomAD database, including 9,842 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 0.35 (9842 hom., cov: 30)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

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]

LOC107987046 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.92-2439C>T		intron_variant		ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.92-2439C>T		intron_variant			NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53495 AN: 151614 Hom.: 9825 Cov.: 30

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.353 AC: 53535 AN: 151732 Hom.: 9842 Cov.: 30 AF XY: 0.360 AC XY: 26671 AN XY: 74152

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.347

Alfa AF: 0.223 Hom.: 499

Bravo AF: 0.362

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs11792633; hg19: chr9-6248035; COSMIC: COSV67343554;