9-6247693-G-A

Variant names:

• chr9-6247693-G-A
• rs10975516
• NM_033439.4:c.92-2781G>A

Variant summary

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

The NM_033439.4(IL33):​c.92-2781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,792 control chromosomes in the GnomAD database, including 13,668 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 0.41 (13668 hom., cov: 30)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 9 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	NM_033439.4	MANE Select	c.92-2781G>A		intron	N/A	NP_254274.1
	IL33	NM_001314044.2		c.92-2781G>A		intron	N/A	NP_001300973.1
	IL33	NM_001314045.2		c.92-2781G>A		intron	N/A	NP_001300974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.92-2781G>A		intron	N/A	ENSP00000507310.1
	IL33	ENST00000381434.7	TSL:1	c.92-2781G>A		intron	N/A	ENSP00000370842.3
	IL33	ENST00000611532.4	TSL:1	c.92-2781G>A		intron	N/A	ENSP00000478858.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61826 AN: 151674 Hom.: 13630 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.408 AC: 61913 AN: 151792 Hom.: 13668 Cov.: 30 AF XY: 0.413 AC XY: 30593 AN XY: 74138

African (AFR) AF: 0.555 AC: 22949 AN: 41386

American (AMR) AF: 0.495 AC: 7540 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3466

East Asian (EAS) AF: 0.496 AC: 2552 AN: 5148

South Asian (SAS) AF: 0.405 AC: 1945 AN: 4804

European-Finnish (FIN) AF: 0.342 AC: 3593 AN: 10510

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21223 AN: 67918

Other (OTH) AF: 0.396 AC: 834 AN: 2108

Alfa AF: 0.337 Hom.: 15082

Bravo AF: 0.425

Asia WGS AF: 0.417 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.21
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: rs10975516; hg19: chr9-6247693; COSMIC: COSV67343547; COSMIC: COSV67343547;