rs734005

Positions:

• chr7-148808772-G-A
• chr7-148808772-G-C
• chr7-148808772-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004456.5(EZH2):​c.2195+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,122 control chromosomes in the GnomAD database, including 38,442 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 0.70 (38442 hom., cov: 32)
• Consequence: EZH2 NM_004456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EZH2	NM_004456.5	c.2195+299C>T		intron_variant		ENST00000320356.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZH2	ENST00000320356.7	c.2195+299C>T		intron_variant		1	NM_004456.5	P4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106112 AN: 152004 Hom.: 38393 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.698 AC: 106223 AN: 152122 Hom.: 38442 Cov.: 32 AF XY: 0.695 AC XY: 51679 AN XY: 74358

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.666

Alfa AF: 0.497 Hom.: 1214

Bravo AF: 0.719

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs734005; hg19: chr7-148505864;