Variant chr7-148846601-TA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004456.5(EZH2):c.118-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43236 hom., cov: 0)

Exomes 𝑓: 0.68 ( 272215 hom. )

Consequence

EZH2
NM_004456.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.476

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-148846601-TA-T is Benign according to our data. Variant chr7-148846601-TA-T is described in ClinVar as [Benign]. Clinvar id is 210966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-148846601-TA-T is described in Lovd as [Benign]. Variant chr7-148846601-TA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EZH2	NM_004456.5 linkuse as main transcript	c.118-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7 linkuse as main transcript	c.118-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004456.5	ENSP00000320147	P4	Q15910-2

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

112887

AN:

150286

Hom.:

43186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.732

GnomAD3 exomes

AF:

0.701

AC:

140067

AN:

199860

Hom.:

44499

AF XY:

0.694

AC XY:

74716

AN XY:

107628

show subpopulations

Gnomad AFR exome

AF:

0.905

Gnomad AMR exome

AF:

0.718

Gnomad ASJ exome

AF:

0.693

Gnomad EAS exome

AF:

0.673

Gnomad SAS exome

AF:

0.676

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.692

Gnomad OTH exome

AF:

0.692

GnomAD4 exome

AF:

0.676

AC:

874854

AN:

1294816

Hom.:

272215

Cov.:

AF XY:

0.676

AC XY:

435388

AN XY:

644354

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.708

Gnomad4 ASJ exome

AF:

0.679

Gnomad4 EAS exome

AF:

0.659

Gnomad4 SAS exome

AF:

0.663

Gnomad4 FIN exome

AF:

0.620

Gnomad4 NFE exome

AF:

0.672

Gnomad4 OTH exome

AF:

0.685

GnomAD4 genome

AF:

0.751

AC:

112998

AN:

150404

Hom.:

43236

Cov.:

AF XY:

0.748

AC XY:

54870

AN XY:

73344

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.749

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.670

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.599

Gnomad4 NFE

AF:

0.686

Gnomad4 OTH

AF:

0.733

Bravo

AF:

0.768

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Weaver syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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