Genetic Variant EZR:c.1597-18T>C (chr6-158767096-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001111077.2(EZR):c.1597-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,613,162 control chromosomes in the GnomAD database, including 416,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.66 ( 34245 hom., cov: 31)

Exomes 𝑓: 0.71 ( 382113 hom. )

Consequence

EZR
NM_001111077.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-158767096-A-G is Benign according to our data. Variant chr6-158767096-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EZR	NM_001111077.2 link	c.1597-18T>C	intron_variant	Intron 13 of 13	ENST00000367075.4	NP_001104547.1	P15311
EZR	NM_003379.5 link	c.1597-18T>C	intron_variant	Intron 12 of 12		NP_003370.2	P15311
EZR	XM_011536110.2 link	c.1189-18T>C	intron_variant	Intron 9 of 9		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4 link	c.1597-18T>C		intron_variant	Intron 13 of 13	1	NM_001111077.2	ENSP00000356042.3		P15311
EZR	ENST00000337147.11 link	c.1597-18T>C		intron_variant	Intron 12 of 12	1		ENSP00000338934.7		P15311

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100023

AN:

151862

Hom.:

34211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.622

GnomAD3 exomes

AF:

0.622

AC:

154861

AN:

248852

Hom.:

52920

AF XY:

0.635

AC XY:

85481

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.633

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.738

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.712

AC:

1039757

AN:

1461182

Hom.:

382113

Cov.:

AF XY:

0.710

AC XY:

516261

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.819

Gnomad4 NFE exome

AF:

0.754

Gnomad4 OTH exome

AF:

0.666

GnomAD4 genome

AF:

0.659

AC:

100125

AN:

151980

Hom.:

34245

Cov.:

AF XY:

0.654

AC XY:

48581

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.628

Gnomad4 FIN

AF:

0.819

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.622

Alfa

AF:

0.689

Hom.:

7439

Bravo

AF:

0.622

Asia WGS

AF:

0.442

AC:

1539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.29

DANN

Benign

0.66

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over