rs773034103

chr6-158767435-T-Achr6-158767435-T-Cchr6-158767435-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001111077.2(EZR):c.1422A>T(p.Pro474=) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35

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 -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 GnomAd at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EZR	NM_001111077.2	c.1422A>T	p.Pro474=	synonymous_variant	13/14	ENST00000367075.4
EZR	NM_003379.5	c.1422A>T	p.Pro474=	synonymous_variant	12/13
EZR	XM_011536110.2	c.1014A>T	p.Pro338=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZR	ENST00000367075.4	c.1422A>T	p.Pro474=	synonymous_variant	13/14	1	NM_001111077.2	P1
EZR	ENST00000337147.11	c.1422A>T	p.Pro474=	synonymous_variant	12/13	1		P1

Frequencies

GnomAD3 genomes AF: 0.000297 AC: 40 AN: 134688 Hom.: 0 Cov.: 31

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: 34 AN: 229422 Hom.: 0 AF XY: 0.000120 AC XY: 15 AN XY: 125362

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.: 1 Cov.: 42 AF XY: 0.000198 AC XY: 123 AN XY: 619776

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: 40 AN: 134688 Hom.: 0 Cov.: 31 AF XY: 0.000246 AC XY: 16 AN XY: 64992

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.: 0

Bravo AF: 0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 25, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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

Other links and lift over

dbSNP: rs773034103; hg19: chr6-159188467;