rs6950683

Variant names:

• chr7-148884496-T-C
• rs6950683
• NM_004456.5:c.-340A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-148884496-T-C
• chr7-148884496-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004456.5(EZH2):​c.-340A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 151,502 control chromosomes in the GnomAD database, including 57,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (57006 hom., cov: 31)
• Consequence: EZH2 NM_004456.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• Weaver syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZH2	NM_004456.5	c.-340A>G		upstream_gene_variant		ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7	c.-340A>G		upstream_gene_variant		1	NM_004456.5	ENSP00000320147.2

Frequencies

GnomAD3 genomes AF: 0.865 AC: 130916 AN: 151394 Hom.: 56951 Cov.: 31

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.913

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.873

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.865 AC: 131026 AN: 151502 Hom.: 57006 Cov.: 31 AF XY: 0.861 AC XY: 63732 AN XY: 74024

African (AFR) AF: 0.963 AC: 39935 AN: 41462

American (AMR) AF: 0.889 AC: 13547 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2986 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3857 AN: 5050

South Asian (SAS) AF: 0.804 AC: 3877 AN: 4822

European-Finnish (FIN) AF: 0.735 AC: 7641 AN: 10402

Middle Eastern (MID) AF: 0.921 AC: 267 AN: 290

European-Non Finnish (NFE) AF: 0.832 AC: 56351 AN: 67752

Other (OTH) AF: 0.874 AC: 1838 AN: 2102

Alfa AF: 0.833 Hom.: 6180

Bravo AF: 0.879

Asia WGS AF: 0.793 AC: 2712 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.24
PhyloP100		-0.43
PromoterAI		0.035	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6950683; hg19: chr7-148581588; COSMIC: COSV57446838;