rs10975514

Variant names:

• chr9-6246144-G-A
• rs10975514
• NM_033439.4:c.92-4330G>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.92-4330G>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
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	NM_033439.4	MANE Select	c.92-4330G>A		intron	N/A	NP_254274.1	O95760-1
	IL33	NM_001314044.2		c.92-4330G>A		intron	N/A	NP_001300973.1	O95760-1
	IL33	NM_001314045.2		c.92-4330G>A		intron	N/A	NP_001300974.1	O95760-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.92-4330G>A		intron	N/A	ENSP00000507310.1	O95760-1
	IL33	ENST00000381434.7	TSL:1	c.92-4330G>A		intron	N/A	ENSP00000370842.3	O95760-1
	IL33	ENST00000611532.4	TSL:1	c.92-4330G>A		intron	N/A	ENSP00000478858.1	O95760-3

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

African (AFR) AF: 0.372 AC: 14967 AN: 40244

American (AMR) AF: 0.458 AC: 6715 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 942 AN: 3452

East Asian (EAS) AF: 0.500 AC: 2536 AN: 5072

South Asian (SAS) AF: 0.403 AC: 1905 AN: 4724

European-Finnish (FIN) AF: 0.339 AC: 3231 AN: 9544

Middle Eastern (MID) AF: 0.417 AC: 121 AN: 290

European-Non Finnish (NFE) AF: 0.312 AC: 21066 AN: 67582

Other (OTH) AF: 0.353 AC: 721 AN: 2044

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.18
PhyloP100		-0.86
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10975514;

hg19: chr9-6246144;

COSMIC: COSV67343539;

COSMIC: COSV67343539;