9-6256292-G-T

Variant names:

• chr9-6256292-G-T
• rs1048274
• NM_033439.4:c.*124G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033439.4(IL33):​c.*124G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL33 NM_033439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.*124G>T		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.*124G>T		3_prime_UTR_variant	Exon 8 of 8		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 505882 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 266012

African (AFR) AF: 0.00 AC: 0 AN: 13376

American (AMR) AF: 0.00 AC: 0 AN: 19198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14364

East Asian (EAS) AF: 0.00 AC: 0 AN: 31802

South Asian (SAS) AF: 0.00 AC: 0 AN: 43694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2074

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 317388

Other (OTH) AF: 0.00 AC: 0 AN: 27704

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.78
PhyloP100		0.18

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: rs1048274; hg19: chr9-6256292;