rs147319809
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004456.5(EZH2):c.474C>T(p.His158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 1,608,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 1 hom. )
Consequence
EZH2
NM_004456.5 synonymous
NM_004456.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.560
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 7-148829738-G-A is Benign according to our data. Variant chr7-148829738-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416829.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.56 with no splicing effect.
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EZH2 | NM_004456.5 | c.474C>T | p.His158= | synonymous_variant | 5/20 | ENST00000320356.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EZH2 | ENST00000320356.7 | c.474C>T | p.His158= | synonymous_variant | 5/20 | 1 | NM_004456.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000790 AC: 12AN: 151852Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000118 AC: 29AN: 246544Hom.: 0 AF XY: 0.000158 AC XY: 21AN XY: 133202
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GnomAD4 exome AF: 0.0000748 AC: 109AN: 1456610Hom.: 1 Cov.: 30 AF XY: 0.0000745 AC XY: 54AN XY: 724428
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GnomAD4 genome ? AF: 0.0000790 AC: 12AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74242
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Weaver syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at