Genetic Variant NM_001111077.2:c.1422A>T (chr6-158767435-T-A) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001111077.2(EZR):c.1422A>T(p.Pro474Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,375,586 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 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

EZR
NM_001111077.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.35

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 6-158767435-T-A is Benign according to our data. Variant chr6-158767435-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 435105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZR	NM_001111077.2 link	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 13 of 14	ENST00000367075.4	NP_001104547.1	P15311
EZR	NM_003379.5 link	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 12 of 13		NP_003370.2	P15311
EZR	XM_011536110.2 link	c.1014A>T	p.Pro338Pro	synonymous_variant	Exon 9 of 10		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4 link	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 13 of 14	1	NM_001111077.2	ENSP00000356042.3		P15311
EZR	ENST00000337147.11 link	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 12 of 13	1		ENSP00000338934.7		P15311

Frequencies

GnomAD3 genomes

AF:

0.000297

AC:

AN:

134688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000119

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000541

Gnomad OTH

AF:

0.00107

GnomAD3 exomes

AF:

0.000148

AC:

AN:

229422

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

125362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000300

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000532

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000178

AC:

221

AN:

1240898

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

123

AN XY:

619776

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000296

Gnomad4 ASJ exome

AF:

0.0000496

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000153

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.000297

AC:

AN:

134688

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

AN XY:

64992

show subpopulations

Gnomad4 AFR

AF:

0.0000281

Gnomad4 AMR

AF:

0.000150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000119

Gnomad4 NFE

AF:

0.000541

Gnomad4 OTH

AF:

0.00107

Alfa

AF:

0.000622

Hom.:

Bravo

AF:

0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.012

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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