rs12000491

Variant names:

• chr9-6257367-T-C
• rs12000491
• NM_033439.4:c.*1199T>C

Variant summary

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

The NM_033439.4(IL33):​c.*1199T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,612 control chromosomes in the GnomAD database, including 980 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 0.078 (980 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: IL33 NM_033439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.*1199T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.*1199T>C		3_prime_UTR_variant	Exon 8 of 8		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11784 AN: 152134 Hom.: 971 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0417 AC: 15 AN: 360 Hom.: 0 Cov.: 0 AF XY: 0.0348 AC XY: 8 AN XY: 230

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0429 AC: 15 AN: 350

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0777 AC: 11826 AN: 152252 Hom.: 980 Cov.: 32 AF XY: 0.0749 AC XY: 5575 AN XY: 74454

African (AFR) AF: 0.206 AC: 8551 AN: 41498

American (AMR) AF: 0.0383 AC: 586 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4830

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1940 AN: 68026

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0488 Hom.: 535

Bravo AF: 0.0834

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.0
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: rs12000491; hg19: chr9-6257367;