6-158767438-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001111077.2(EZR):c.1419A>C(p.Pro473=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EZR NM_001111077.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.03

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-158767438-T-G is Benign according to our data. Variant chr6-158767438-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 435106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.03 with no splicing effect.
• BS2: High AC in GnomAdExome at 699 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EZR	NM_001111077.2	c.1419A>C	p.Pro473=	synonymous_variant	13/14	ENST00000367075.4
EZR	NM_003379.5	c.1419A>C	p.Pro473=	synonymous_variant	12/13
EZR	XM_011536110.2	c.1011A>C	p.Pro337=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZR	ENST00000367075.4	c.1419A>C	p.Pro473=	synonymous_variant	13/14	1	NM_001111077.2	P1
EZR	ENST00000337147.11	c.1419A>C	p.Pro473=	synonymous_variant	12/13	1		P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 33 AN: 137854 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000145

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.000233

Gnomad SAS AF: 0.000250

Gnomad FIN AF: 0.000114

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000519

GnomAD3 exomes AF: 0.00300 AC: 699 AN: 233284 Hom.: 0 AF XY: 0.00272 AC XY: 346 AN XY: 127058

Gnomad AFR exome AF: 0.00104

Gnomad AMR exome AF: 0.00942

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00174

Gnomad SAS exome AF: 0.000205

Gnomad FIN exome AF: 0.00286

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.00471

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00145 AC: 1581 AN: 1090228 Hom.: 0 Cov.: 38 AF XY: 0.00153 AC XY: 838 AN XY: 546406

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.00779

Gnomad4 EAS exome AF: 0.000624

Gnomad4 SAS exome AF: 0.000346

Gnomad4 FIN exome AF: 0.00286

Gnomad4 NFE exome AF: 0.000796

Gnomad4 OTH exome AF: 0.00226

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000239 AC: 33 AN: 137952 Hom.: 0 Cov.: 31 AF XY: 0.000224 AC XY: 15 AN XY: 66866

Gnomad4 AFR AF: 0.000273

Gnomad4 AMR AF: 0.000145

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.000233

Gnomad4 SAS AF: 0.000250

Gnomad4 FIN AF: 0.000114

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.000514

Alfa AF: 0.00107 Hom.: 0

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 05, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.20
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs776473073; hg19: chr6-159188470;