Variant rs147363431 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000367075.4(EZR):c.795T>G(p.Pro265=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,611,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 0 hom. )

Consequence

EZR
ENST00000367075.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0001586

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-158776408-A-C is Benign according to our data. Variant chr6-158776408-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 435110.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-158776408-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.29 with no splicing effect.

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EZR	NM_001111077.2 linkuse as main transcript	c.795T>G	p.Pro265=	splice_region_variant, synonymous_variant	8/14	ENST00000367075.4	NP_001104547.1
EZR	NM_003379.5 linkuse as main transcript	c.795T>G	p.Pro265=	splice_region_variant, synonymous_variant	7/13		NP_003370.2
EZR	XM_011536110.2 linkuse as main transcript	c.387T>G	p.Pro129=	splice_region_variant, synonymous_variant	4/10		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4 linkuse as main transcript	c.795T>G	p.Pro265=	splice_region_variant, synonymous_variant	8/14	1	NM_001111077.2	ENSP00000356042	P1
EZR	ENST00000337147.11 linkuse as main transcript	c.795T>G	p.Pro265=	splice_region_variant, synonymous_variant	7/13	1		ENSP00000338934	P1

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

125

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000725

AC:

182

AN:

251186

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00148

AC:

2156

AN:

1458870

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1068

AN XY:

725988

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.000680

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152346

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000865

EpiCase

AF:

0.00185

EpiControl

AF:

0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 02, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.2

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.068

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