Variant 9-6252979-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033439.4(IL33):c.457G>T(p.Asp153Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,528,506 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 6 hom. )

Consequence

IL33
NM_033439.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.64

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006285578).

BP6

Variant 9-6252979-G-T is Benign according to our data. Variant chr9-6252979-G-T is described in ClinVar as [Benign]. Clinvar id is 783540.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL33	NM_033439.4 linkuse as main transcript	c.457G>T	p.Asp153Tyr	missense_variant	5/8	ENST00000682010.1
LOC107987046	XR_001746614.2 linkuse as main transcript	n.153-24684C>A		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.457G>T	p.Asp153Tyr	missense_variant	5/8		NM_033439.4	P1	O95760-1

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

640

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00113

AC:

251

AN:

222482

Hom.:

AF XY:

0.000910

AC XY:

110

AN XY:

120852

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.000634

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000945

Gnomad OTH exome

AF:

0.000381

GnomAD4 exome

AF:

0.000383

AC:

527

AN:

1376314

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

241

AN XY:

682564

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000898

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000123

Gnomad4 OTH exome

AF:

0.000808

GnomAD4 genome

AF:

0.00422

AC:

642

AN:

152192

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.00436

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00151

AC:

183

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.9

.;D

REVEL

Benign

0.11

Sift

Uncertain

0.0080

.;D

Sift4G

Uncertain

0.039

D;T

Polyphen

0.98

.;D

Vest4

0.48

MVP

0.59

MPC

0.018

ClinPred

0.086

GERP RS

-6.0

Varity_R

0.39

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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