7-148808210-C-T

Position:

• chr7-148808210-C-T

Variant summary

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

The NM_004456.5(EZH2):​c.2196-504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,198 control chromosomes in the GnomAD database, including 40,353 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 0.73 (40353 hom., cov: 33)
• Consequence: EZH2 NM_004456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EZH2	NM_004456.5	c.2196-504G>A		intron_variant		ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7	c.2196-504G>A		intron_variant		1	NM_004456.5	ENSP00000320147.2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110473 AN: 152080 Hom.: 40329 Cov.: 33

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.726 AC: 110553 AN: 152198 Hom.: 40353 Cov.: 33 AF XY: 0.722 AC XY: 53726 AN XY: 74406

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.720

Alfa AF: 0.710 Hom.: 4878

Bravo AF: 0.739

Asia WGS AF: 0.671 AC: 2333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.44

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: rs887569; hg19: chr7-148505302;