rs773034103

Variant names:

• chr6-158767435-T-A
• rs773034103
• NM_001111077.2:c.1422A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-158767435-T-A
• chr6-158767435-T-C
• chr6-158767435-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZR	NM_001111077.2	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 13 of 14	ENST00000367075.4	NP_001104547.1
EZR	NM_003379.5	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 12 of 13		NP_003370.2
EZR	XM_011536110.2	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	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 13 of 14	1	NM_001111077.2	ENSP00000356042.3
EZR	ENST00000337147.11	c.1422A>T	p.Pro474Pro	synonymous_variant	Exon 12 of 13	1		ENSP00000338934.7

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

GnomAD2 exomes AF: 0.000148 AC: 34 AN: 229422 AF XY: 0.000120

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 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

African (AFR) AF: 0.00 AC: 0 AN: 27650

American (AMR) AF: 0.000296 AC: 11 AN: 37110

Ashkenazi Jewish (ASJ) AF: 0.0000496 AC: 1 AN: 20176

East Asian (EAS) AF: 0.00 AC: 0 AN: 26924

South Asian (SAS) AF: 0.00 AC: 0 AN: 80886

European-Finnish (FIN) AF: 0.000153 AC: 6 AN: 39226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4846

European-Non Finnish (NFE) AF: 0.000207 AC: 198 AN: 955216

Other (OTH) AF: 0.000102 AC: 5 AN: 48864

GnomAD4 genome AF: 0.000297 AC: 40 AN: 134688 Hom.: 0 Cov.: 31 AF XY: 0.000246 AC XY: 16 AN XY: 64992

African (AFR) AF: 0.0000281 AC: 1 AN: 35634

American (AMR) AF: 0.000150 AC: 2 AN: 13376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3254

East Asian (EAS) AF: 0.00 AC: 0 AN: 4296

South Asian (SAS) AF: 0.00 AC: 0 AN: 3908

European-Finnish (FIN) AF: 0.000119 AC: 1 AN: 8408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000541 AC: 34 AN: 62792

Other (OTH) AF: 0.00107 AC: 2 AN: 1872

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

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
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs773034103; hg19: chr6-159188467;