Variant 9-6254551-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033439.4(IL33):c.610G>A(p.Glu204Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL33
NM_033439.4 missense, splice_region

Scores

Splicing: ADA: 0.0001554

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.128

Variant links:

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]

IL33 links:

LOC107987046 (HGNC:):

LOC107987046 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19491264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant, splice_region_variant	7/8	ENST00000682010.1
LOC107987046	XR_001746614.2 linkuse as main transcript	n.153-26256C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL33	ENST00000682010.1 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant, splice_region_variant	7/8		NM_033439.4	P1	O95760-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143880

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703620

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

143880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70288

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.610G>A (p.E204K) alteration is located in exon 7 (coding exon 6) of the IL33 gene. This alteration results from a G to A substitution at nucleotide position 610, causing the glutamic acid (E) at amino acid position 204 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

0.67

D;D;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.6

D;.;D;D

REVEL

Benign

0.040

Sift

Benign

0.12

T;.;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.34

.;.;B;.

Vest4

0.30

MutPred

0.35

.;.;Gain of ubiquitination at E204 (P = 0.0219);.;

MVP

0.50

MPC

0.0058

ClinPred

0.18

GERP RS

0.81

Varity_R

0.20

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.052

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over