rs7025417

chr9-6240084-T-Cchr9-6240084-T-G

Variant summary

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

The NM_033439.4(IL33):c.-11-1600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,130 control chromosomes in the GnomAD database, including 4,023 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 0.22 (4023 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.-11-1600T>C		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-11789A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.-11-1600T>C		intron_variant			NM_033439.4	P1
IL33	ENST00000417746.6	c.-11-1600T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33624 AN: 152010 Hom.: 4005 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.221 AC: 33647 AN: 152130 Hom.: 4023 Cov.: 32 AF XY: 0.220 AC XY: 16370 AN XY: 74358

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.190

Alfa AF: 0.208 Hom.: 2848

Bravo AF: 0.217

Asia WGS AF: 0.383 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.1
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7025417; hg19: chr9-6240084;