7-148811741-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004456.5(EZH2):​c.1852-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,595,956 control chromosomes in the GnomAD database, including 355,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34810 hom., cov: 31)
Exomes 𝑓: 0.67 ( 320846 hom. )

Consequence

EZH2
NM_004456.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.352
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 7-148811741-A-G is Benign according to our data. Variant chr7-148811741-A-G is described in ClinVar as [Benign]. Clinvar id is 670472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-148811741-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EZH2NM_004456.5 linkc.1852-21T>C intron_variant Intron 15 of 19 ENST00000320356.7 NP_004447.2 Q15910-2A0A090N8E9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EZH2ENST00000320356.7 linkc.1852-21T>C intron_variant Intron 15 of 19 1 NM_004456.5 ENSP00000320147.2 Q15910-2

Frequencies

GnomAD3 genomes
AF:
0.675
AC:
102472
AN:
151810
Hom.:
34787
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.709
Gnomad AMI
AF:
0.586
Gnomad AMR
AF:
0.724
Gnomad ASJ
AF:
0.675
Gnomad EAS
AF:
0.672
Gnomad SAS
AF:
0.614
Gnomad FIN
AF:
0.564
Gnomad MID
AF:
0.715
Gnomad NFE
AF:
0.666
Gnomad OTH
AF:
0.677
GnomAD3 exomes
AF:
0.669
AC:
162544
AN:
243020
Hom.:
54502
AF XY:
0.664
AC XY:
87729
AN XY:
132162
show subpopulations
Gnomad AFR exome
AF:
0.707
Gnomad AMR exome
AF:
0.728
Gnomad ASJ exome
AF:
0.679
Gnomad EAS exome
AF:
0.668
Gnomad SAS exome
AF:
0.615
Gnomad FIN exome
AF:
0.590
Gnomad NFE exome
AF:
0.671
Gnomad OTH exome
AF:
0.663
GnomAD4 exome
AF:
0.666
AC:
961145
AN:
1444028
Hom.:
320846
Cov.:
26
AF XY:
0.664
AC XY:
477616
AN XY:
719260
show subpopulations
Gnomad4 AFR exome
AF:
0.717
Gnomad4 AMR exome
AF:
0.728
Gnomad4 ASJ exome
AF:
0.682
Gnomad4 EAS exome
AF:
0.660
Gnomad4 SAS exome
AF:
0.619
Gnomad4 FIN exome
AF:
0.591
Gnomad4 NFE exome
AF:
0.668
Gnomad4 OTH exome
AF:
0.662
GnomAD4 genome
AF:
0.675
AC:
102549
AN:
151928
Hom.:
34810
Cov.:
31
AF XY:
0.671
AC XY:
49866
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.709
Gnomad4 AMR
AF:
0.725
Gnomad4 ASJ
AF:
0.675
Gnomad4 EAS
AF:
0.672
Gnomad4 SAS
AF:
0.614
Gnomad4 FIN
AF:
0.564
Gnomad4 NFE
AF:
0.666
Gnomad4 OTH
AF:
0.679
Alfa
AF:
0.668
Hom.:
7360
Bravo
AF:
0.692
Asia WGS
AF:
0.657
AC:
2286
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 19, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Weaver syndrome Benign:1
Aug 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.46
DANN
Benign
0.59

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.

Other links and lift over

dbSNP: rs2072407; hg19: chr7-148508833; COSMIC: COSV57445837; API