rs10975514

chr9-6246144-G-A

Variant summary

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

The NM_033439.4(IL33):c.92-4330G>A 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 148,504 control chromosomes in the GnomAD database, including 9,602 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 (9602 hom., cov: 27)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.92-4330G>A		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-17849C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.92-4330G>A		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 52360 AN: 148406 Hom.: 9586 Cov.: 27

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.353 AC: 52395 AN: 148504 Hom.: 9602 Cov.: 27 AF XY: 0.359 AC XY: 25931 AN XY: 72190

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.353

Alfa AF: 0.340 Hom.: 2089

Bravo AF: 0.364

Asia WGS AF: 0.407 AC: 1412 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.0
Dann	Benign	0.18

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: rs10975514; hg19: chr9-6246144; COSMIC: COSV67343539; COSMIC: COSV67343539;