rs773034103
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.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
NM_001111077.2 synonymous
Scores
2
Clinical Significance
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]
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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/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: 40AN: 134688Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000148 AC: 34AN: 229422Hom.: 0 AF XY: 0.000120 AC XY: 15AN XY: 125362
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GnomAD4 exome AF: 0.000178 AC: 221AN: 1240898Hom.: 1 Cov.: 42 AF XY: 0.000198 AC XY: 123AN XY: 619776
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GnomAD4 genome ? AF: 0.000297 AC: 40AN: 134688Hom.: 0 Cov.: 31 AF XY: 0.000246 AC XY: 16AN XY: 64992
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at