9-6251012-C-T

Variant names:

• chr9-6251012-C-T
• rs1317230
• NM_033439.4:c.218-128C>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.218-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,057,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 11 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=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	NM_033439.4	MANE Select	c.218-128C>T		intron	N/A	NP_254274.1	O95760-1
	IL33	NM_001314044.2		c.218-128C>T		intron	N/A	NP_001300973.1	O95760-1
	IL33	NM_001314045.2		c.218-128C>T		intron	N/A	NP_001300974.1	O95760-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL33	ENST00000682010.1	MANE Select	c.218-128C>T		intron	N/A	ENSP00000507310.1	O95760-1
	IL33	ENST00000381434.7	TSL:1	c.218-128C>T		intron	N/A	ENSP00000370842.3	O95760-1
	IL33	ENST00000611532.4	TSL:1	c.217+413C>T		intron	N/A	ENSP00000478858.1	O95760-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1057836 Hom.: 0 AF XY: 0.00000190 AC XY: 1 AN XY: 527298

African (AFR) AF: 0.00 AC: 0 AN: 24512

American (AMR) AF: 0.00 AC: 0 AN: 25848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17976

East Asian (EAS) AF: 0.00 AC: 0 AN: 35936

South Asian (SAS) AF: 0.00 AC: 0 AN: 60036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3128

European-Non Finnish (NFE) AF: 0.00000124 AC: 1 AN: 809544

Other (OTH) AF: 0.00 AC: 0 AN: 45622

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.22
PhyloP100		-1.7

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: rs1317230; hg19: chr9-6251012;