rs1317230

chr9-6251012-C-Achr9-6251012-C-Gchr9-6251012-C-T

Variant summary

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

The NM_033439.4(IL33):c.218-128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,206,902 control chromosomes in the GnomAD database, including 53,029 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 0.27 (6425 hom., cov: 31)
  • Exomes 𝑓: 0.29 (46604 hom.)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.218-128C>A		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-22717G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.218-128C>A		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41560 AN: 151722 Hom.: 6422 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.288 AC: 303679 AN: 1055062 Hom.: 46604 AF XY: 0.291 AC XY: 153016 AN XY: 525884

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.274 AC: 41560 AN: 151840 Hom.: 6425 Cov.: 31 AF XY: 0.283 AC XY: 21008 AN XY: 74192

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.284

Alfa AF: 0.250 Hom.: 1467

Bravo AF: 0.278

Asia WGS AF: 0.375 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.29
Dann	Benign	0.28

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: rs1317230; hg19: chr9-6251012; COSMIC: COSV67343560;