rs7035413

Variant names:

• chr9-6243119-A-G
• rs7035413
• NM_033439.4:c.91+1334A>G

Variant summary

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

The NM_033439.4(IL33):​c.91+1334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,138 control chromosomes in the GnomAD database, including 2,759 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 0.18 (2759 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 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.91+1334A>G		intron	N/A	NP_254274.1
	IL33	NM_001314044.2		c.91+1334A>G		intron	N/A	NP_001300973.1
	IL33	NM_001314045.2		c.91+1334A>G		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.91+1334A>G		intron	N/A	ENSP00000507310.1
	IL33	ENST00000381434.7	TSL:1	c.91+1334A>G		intron	N/A	ENSP00000370842.3
	IL33	ENST00000611532.4	TSL:1	c.91+1334A>G		intron	N/A	ENSP00000478858.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27185 AN: 152020 Hom.: 2759 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.179 AC: 27186 AN: 152138 Hom.: 2759 Cov.: 32 AF XY: 0.178 AC XY: 13211 AN XY: 74372

African (AFR) AF: 0.118 AC: 4908 AN: 41514

American (AMR) AF: 0.167 AC: 2542 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.172 AC: 830 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2255 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15071 AN: 67988

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.178 Hom.: 356

Bravo AF: 0.175

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.58
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

Other links and lift over

dbSNP: rs7035413; hg19: chr9-6243119;