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GeneBe

6-158767417-C-T

Variant summary

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

The NM_001111077.2(EZR):c.1440G>A(p.Pro480=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,576,582 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

EZR
NM_001111077.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.85
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-158767417-C-T is Benign according to our data. Variant chr6-158767417-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719278.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.85 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 66 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EZRNM_001111077.2 linkuse as main transcriptc.1440G>A p.Pro480= synonymous_variant 13/14 ENST00000367075.4
EZRNM_003379.5 linkuse as main transcriptc.1440G>A p.Pro480= synonymous_variant 12/13
EZRXM_011536110.2 linkuse as main transcriptc.1032G>A p.Pro344= synonymous_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EZRENST00000367075.4 linkuse as main transcriptc.1440G>A p.Pro480= synonymous_variant 13/141 NM_001111077.2 P1
EZRENST00000337147.11 linkuse as main transcriptc.1440G>A p.Pro480= synonymous_variant 12/131 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000438
AC:
66
AN:
150776
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000213
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000621
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000375
AC:
94
AN:
250478
Hom.:
0
AF XY:
0.000384
AC XY:
52
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.000551
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000610
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000547
AC:
780
AN:
1425698
Hom.:
1
Cov.:
48
AF XY:
0.000524
AC XY:
372
AN XY:
709804
show subpopulations
Gnomad4 AFR exome
AF:
0.000245
Gnomad4 AMR exome
AF:
0.000454
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000366
Gnomad4 SAS exome
AF:
0.0000933
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000639
Gnomad4 OTH exome
AF:
0.000615
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000437
AC:
66
AN:
150884
Hom.:
0
Cov.:
32
AF XY:
0.000339
AC XY:
25
AN XY:
73740
show subpopulations
Gnomad4 AFR
AF:
0.000170
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000213
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000621
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000400
Hom.:
0
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000415

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
0.079
Dann
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs192713832; hg19: chr6-159188449; API