6-158767435-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001111077.2(EZR):c.1422A>C(p.Pro474=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P474P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EZR NM_001111077.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.
• BS2: High AC in GnomAdExome at 372 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 29 AN: 134674 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000842

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000299

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.000233

Gnomad SAS AF: 0.000256

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000303

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00162 AC: 372 AN: 229422 Hom.: 0 AF XY: 0.00154 AC XY: 193 AN XY: 125362

Gnomad AFR exome AF: 0.000333

Gnomad AMR exome AF: 0.000700

Gnomad ASJ exome AF: 0.00136

Gnomad EAS exome AF: 0.000232

Gnomad SAS exome AF: 0.0000340

Gnomad FIN exome AF: 0.00585

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00126

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000267 AC: 331 AN: 1240260 Hom.: 0 Cov.: 42 AF XY: 0.000297 AC XY: 184 AN XY: 619462

Gnomad4 AFR exome AF: 0.000471

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.000943

Gnomad4 EAS exome AF: 0.000149

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.00128

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.000205

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000215 AC: 29 AN: 134720 Hom.: 0 Cov.: 31 AF XY: 0.000261 AC XY: 17 AN XY: 65048

Gnomad4 AFR AF: 0.0000840

Gnomad4 AMR AF: 0.000299

Gnomad4 ASJ AF: 0.000307

Gnomad4 EAS AF: 0.000234

Gnomad4 SAS AF: 0.000257

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000303

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000732 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.017
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV51908507; COSMIC: COSV51908507;