Variant 7-148814079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004456.5(EZH2):c.1731G>A(p.Pro577Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,614,132 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 10 hom., cov: 32)

Exomes 𝑓: 0.015 ( 210 hom. )

Consequence

EZH2
NM_004456.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.07

Variant links:

Genes affected

EZH2 (HGNC:3527): (enhancer of zeste 2 polycomb repressive complex 2 subunit) This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

EZH2 links:

EZH2 (HGNC:):

EZH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-148814079-C-T is Benign according to our data. Variant chr7-148814079-C-T is described in ClinVar as [Benign]. Clinvar id is 158577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-148814079-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1605/152262) while in subpopulation NFE AF= 0.0169 (1147/68032). AF 95% confidence interval is 0.016. There are 10 homozygotes in gnomad4. There are 779 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1605 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EZH2	NM_004456.5 linkuse as main transcript	c.1731G>A	p.Pro577Pro	synonymous_variant	15/20	ENST00000320356.7	NP_004447.2	Q15910-2A0A090N8E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7 linkuse as main transcript	c.1731G>A	p.Pro577Pro	synonymous_variant	15/20	1	NM_004456.5	ENSP00000320147.2		Q15910-2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1605

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0104

AC:

2616

AN:

251346

Hom.:

AF XY:

0.00973

AC XY:

1322

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0156

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0153

AC:

22436

AN:

1461870

Hom.:

210

Cov.:

AF XY:

0.0146

AC XY:

10637

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.0262

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.0105

AC:

1605

AN:

152262

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

779

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0169

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.00897

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Weaver syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.2

DANN

Benign

0.58

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over