rs10975519

Positions:

• chr9-6253571-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.489C>T	p.Tyr163Tyr	synonymous_variant	6/8	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.489C>T	p.Tyr163Tyr	synonymous_variant	6/8		NM_033439.4	ENSP00000507310.1

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

GnomAD3 exomes AF: 0.380 AC: 94377 AN: 248652 Hom.: 19435 AF XY: 0.370 AC XY: 49778 AN XY: 134434

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 SAS exome AF: 0.388

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

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.323

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.349

Alfa AF: 0.324 Hom.: 11209

Bravo AF: 0.365

Asia WGS AF: 0.400 AC: 1388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs10975519; hg19: chr9-6253571; COSMIC: COSV67343121;