rs193920852

Variant names:

• chr9-6256067-G-A
• rs193920852
• NM_033439.4:c.712G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033439.4(IL33):​c.712G>A​(p.Val238Met) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL33 NM_033439.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.624
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08157632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.712G>A	p.Val238Met	missense_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.712G>A	p.Val238Met	missense_variant	Exon 8 of 8		NM_033439.4	ENSP00000507310.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.082	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	.;.;L;.
PhyloP100		0.62
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;.;N;N
REVEL	Benign	0.021
Sift	Uncertain	0.010	D;.;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.19	.;.;B;.
Vest4		0.077
MutPred		0.25		.;.;Loss of catalytic residue at V238 (P = 0.0138);.;
MVP		0.092
MPC		0.0076
ClinPred		0.15	T
GERP RS		0.35
Varity_R		0.29
gMVP		0.13
Mutation Taster		=78/22	polymorphism

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: rs193920852; hg19: chr9-6256067; COSMIC: COSV67342955;