9-6253560-T-A

Position:

• chr9-6253560-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033439.4(IL33):​c.478T>A​(p.Leu160Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL33 NM_033439.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.338

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15304464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL33	NM_033439.4	c.478T>A	p.Leu160Ile	missense_variant	6/8	ENST00000682010.1	NP_254274.1
LOC107987046	XR_001746614.2	n.153-25265A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.478T>A	p.Leu160Ile	missense_variant	6/8		NM_033439.4	ENSP00000507310	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.478T>A (p.L160I) alteration is located in exon 6 (coding exon 5) of the IL33 gene. This alteration results from a T to A substitution at nucleotide position 478, causing the leucine (L) at amino acid position 160 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;.;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	.;.;L;.
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;.;N;N
REVEL	Benign	0.082
Sift	Uncertain	0.016	D;.;D;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.71	.;.;P;.
Vest4		0.34
MutPred		0.31		.;.;Gain of methylation at K156 (P = 0.0474);.;
MVP		0.24
MPC		0.025
ClinPred		0.60	D
GERP RS		0.72
Varity_R		0.18
gMVP		0.033

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-6253560;