Variant chr6-158767445-G-A 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_001111077.2(EZR):c.1412C>T(p.Pro471Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000291 in 1,612,796 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

EZR
NM_001111077.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.43

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008386284).

BP6

Variant 6-158767445-G-A is Benign according to our data. Variant chr6-158767445-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735583.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EZR	NM_001111077.2 linkuse as main transcript	c.1412C>T	p.Pro471Leu	missense_variant	13/14	ENST00000367075.4	NP_001104547.1
EZR	NM_003379.5 linkuse as main transcript	c.1412C>T	p.Pro471Leu	missense_variant	12/13		NP_003370.2
EZR	XM_011536110.2 linkuse as main transcript	c.1004C>T	p.Pro335Leu	missense_variant	9/10		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4 linkuse as main transcript	c.1412C>T	p.Pro471Leu	missense_variant	13/14	1	NM_001111077.2	ENSP00000356042	P1
EZR	ENST00000337147.11 linkuse as main transcript	c.1412C>T	p.Pro471Leu	missense_variant	12/13	1		ENSP00000338934	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000573

AC:

143

AN:

249682

Hom.:

AF XY:

0.000644

AC XY:

AN XY:

135020

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00403

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000292

AC:

426

AN:

1460552

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

253

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000289

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000502

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.79

DEOGEN2

Uncertain

0.44

T;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.89

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.31

T;.;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.0060

B;.;B

Vest4

0.34

MVP

0.66

MPC

0.34

ClinPred

0.049

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.40

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

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