Variant rs139467617 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001111077.2(EZR):c.752A>G(p.Asn251Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000711 in 1,613,692 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00057 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 8 hom. )

Consequence

EZR
NM_001111077.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

EZR (HGNC:12691): (ezrin) The cytoplasmic peripheral membrane protein encoded by this gene functions as a protein-tyrosine kinase substrate in microvilli. As a member of the ERM protein family, this protein serves as an intermediate between the plasma membrane and the actin cytoskeleton. This protein plays a key role in cell surface structure adhesion, migration and organization, and it has been implicated in various human cancers. A pseudogene located on chromosome 3 has been identified for this gene. Alternatively spliced variants have also been described for this gene. [provided by RefSeq, Jul 2008]

EZR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011818022).

BP6

Variant 6-158776451-T-C is Benign according to our data. Variant chr6-158776451-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 87 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EZR	NM_001111077.2 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	8/14	ENST00000367075.4
EZR	NM_003379.5 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	7/13
EZR	XM_011536110.2 linkuse as main transcript	c.344A>G	p.Asn115Ser	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZR	ENST00000367075.4 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	8/14	1	NM_001111077.2	P1
EZR	ENST00000337147.11 linkuse as main transcript	c.752A>G	p.Asn251Ser	missense_variant	7/13	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00124

AC:

312

AN:

250684

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00517

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000726

AC:

1061

AN:

1461364

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

627

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00474

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000427

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000571

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000658

Hom.:

Bravo

AF:

0.000582

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00111

AC:

135

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 24, 2017

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;.;D

Eigen

Benign

-0.21

Eigen_PC

Benign

0.0075

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.17

N;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-4.4

D;.;D

REVEL

Uncertain

0.31

Sift

Benign

0.42

T;.;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.030

B;.;B

Vest4

0.42

MVP

0.61

MPC

0.26

ClinPred

0.063

GERP RS

4.8

Varity_R

0.59

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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