NM_033439.4:c.489C>T

Variant names:

• chr9-6253571-C-T
• rs10975519
• NM_033439.4:c.489C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033439.4(IL33):​c.489C>T​(p.Tyr163Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,598,998 control chromosomes in the GnomAD database, including 88,587 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 (9932 hom., cov: 31)
  • Exomes 𝑓: 0.32 (78655 hom.)
• Consequence: IL33 NM_033439.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 54 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.111 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.489C>T	p.Tyr163Tyr	synonymous	Exon 6 of 8	NP_254274.1
	IL33	NM_001314044.2		c.489C>T	p.Tyr163Tyr	synonymous	Exon 6 of 8	NP_001300973.1
	IL33	NM_001314045.2		c.489C>T	p.Tyr163Tyr	synonymous	Exon 6 of 8	NP_001300974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.489C>T	p.Tyr163Tyr	synonymous	Exon 6 of 8	ENSP00000507310.1
	IL33	ENST00000381434.7	TSL:1	c.489C>T	p.Tyr163Tyr	synonymous	Exon 5 of 7	ENSP00000370842.3
	IL33	ENST00000611532.4	TSL:1	c.363C>T	p.Tyr121Tyr	synonymous	Exon 4 of 6	ENSP00000478858.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53754 AN: 151766 Hom.: 9915 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.380 AC: 94377 AN: 248652 AF XY: 0.370

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.322 AC: 465608 AN: 1447114 Hom.: 78655 Cov.: 30 AF XY: 0.323 AC XY: 232761 AN XY: 720006

African (AFR) AF: 0.387 AC: 12822 AN: 33110

American (AMR) AF: 0.565 AC: 24716 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6958 AN: 25914

East Asian (EAS) AF: 0.463 AC: 18290 AN: 39494

South Asian (SAS) AF: 0.393 AC: 33231 AN: 84562

European-Finnish (FIN) AF: 0.356 AC: 18889 AN: 53026

Middle Eastern (MID) AF: 0.386 AC: 2210 AN: 5722

European-Non Finnish (NFE) AF: 0.299 AC: 329188 AN: 1101690

Other (OTH) AF: 0.323 AC: 19304 AN: 59826

GnomAD4 genome AF: 0.354 AC: 53795 AN: 151884 Hom.: 9932 Cov.: 31 AF XY: 0.360 AC XY: 26742 AN XY: 74198

African (AFR) AF: 0.381 AC: 15758 AN: 41408

American (AMR) AF: 0.462 AC: 7048 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2434 AN: 5154

South Asian (SAS) AF: 0.401 AC: 1925 AN: 4800

European-Finnish (FIN) AF: 0.342 AC: 3602 AN: 10544

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21026 AN: 67934

Other (OTH) AF: 0.349 AC: 737 AN: 2114

Alfa AF: 0.334 Hom.: 16639

Bravo AF: 0.365

Asia WGS AF: 0.400 AC: 1388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.1
DANN	Benign	0.49
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs10975519; hg19: chr9-6253571; COSMIC: COSV67343121;