rs1048274

chr9-6256292-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):c.*124G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 656,900 control chromosomes in the GnomAD database, including 39,517 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 (9892 hom., cov: 32)
  • Exomes 𝑓: 0.34 (29625 hom.)
• Consequence: IL33 NM_033439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.*124G>A		3_prime_UTR_variant	8/8	ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-27997C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.*124G>A		3_prime_UTR_variant	8/8		NM_033439.4	P1
IL33	ENST00000381434.7	c.*124G>A		3_prime_UTR_variant	7/7	1		P1
IL33	ENST00000417746.6	c.*124G>A		3_prime_UTR_variant	5/5	2
IL33	ENST00000456383.3	c.*124G>A		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53687 AN: 151828 Hom.: 9876 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.336 AC: 169915 AN: 504954 Hom.: 29625 Cov.: 6 AF XY: 0.337 AC XY: 89545 AN XY: 265502

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.354 AC: 53726 AN: 151946 Hom.: 9892 Cov.: 32 AF XY: 0.360 AC XY: 26726 AN XY: 74304

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.348

Alfa AF: 0.314 Hom.: 12630

Bravo AF: 0.364

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	7.6
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048274; hg19: chr9-6256292; COSMIC: COSV67343594; COSMIC: COSV67343594;