rs7019575

chr9-6243935-G-Cchr9-6243935-G-T

Variant summary

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

The NM_033439.4(IL33):c.91+2150G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,028 control chromosomes in the GnomAD database, including 11,256 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 (11256 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.91+2150G>C		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-15640C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.91+2150G>C		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55345 AN: 151910 Hom.: 11240 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.364 AC: 55362 AN: 152028 Hom.: 11256 Cov.: 32 AF XY: 0.365 AC XY: 27118 AN XY: 74298

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.365

Alfa AF: 0.228 Hom.: 528

Bravo AF: 0.349

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	3.9
Dann	Benign	0.83

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: rs7019575; hg19: chr9-6243935;