chr9-6255881-T-G

Position:

• chr9-6255881-T-G

Variant summary

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

The NM_033439.4(IL33):​c.613-87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,005,546 control chromosomes in the GnomAD database, including 184,274 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 0.52 (22548 hom., cov: 31)
  • Exomes 𝑓: 0.61 (161726 hom.)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4	c.613-87T>G		intron_variant		ENST00000682010.1
LOC107987046	XR_001746614.2	n.153-27586A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1	c.613-87T>G		intron_variant			NM_033439.4	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79269 AN: 151742 Hom.: 22529 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.609 AC: 519796 AN: 853686 Hom.: 161726 AF XY: 0.610 AC XY: 271593 AN XY: 445120

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.522 AC: 79293 AN: 151860 Hom.: 22548 Cov.: 31 AF XY: 0.521 AC XY: 38651 AN XY: 74208

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.534

Alfa AF: 0.611 Hom.: 28245

Bravo AF: 0.499

Asia WGS AF: 0.576 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.78

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: rs1332290; hg19: chr9-6255881; COSMIC: COSV67342902;