rs7044343

Positions:

• chr9-6254208-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.521-254C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,830 control chromosomes in the GnomAD database, including 22,031 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 (22031 hom., cov: 31)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.521-254C>T		intron_variant		ENST00000682010.1	NP_254274.1
LOC107987046	XR_001746614.2	n.153-25913G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.521-254C>T		intron_variant			NM_033439.4	ENSP00000507310	P1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78421 AN: 151710 Hom.: 22013 Cov.: 31

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.529

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.517 AC: 78442 AN: 151830 Hom.: 22031 Cov.: 31 AF XY: 0.515 AC XY: 38227 AN XY: 74198

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.533

Alfa AF: 0.590 Hom.: 6326

Bravo AF: 0.494

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.93

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: rs7044343; hg19: chr9-6254208; COSMIC: COSV67342885;