7-148808972-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004456.5(EZH2):c.2195+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 917,260 control chromosomes in the GnomAD database, including 227,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39791 hom., cov: 32)
  • Exomes 𝑓: 0.70 (187442 hom.)
• Consequence: EZH2 NM_004456.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0940

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-148808972-A-G is Benign according to our data. Variant chr7-148808972-A-G is described in ClinVar as [Benign]. Clinvar id is 680128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EZH2	NM_004456.5	c.2195+99T>C		intron_variant		ENST00000320356.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EZH2	ENST00000320356.7	c.2195+99T>C		intron_variant		1	NM_004456.5	P4

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109594 AN: 152060 Hom.: 39767 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.699 AC: 534566 AN: 765082 Hom.: 187442 AF XY: 0.696 AC XY: 278269 AN XY: 400048

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.721 AC: 109673 AN: 152178 Hom.: 39791 Cov.: 32 AF XY: 0.718 AC XY: 53440 AN XY: 74394

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.705

Alfa AF: 0.682 Hom.: 7185

Bravo AF: 0.732

Asia WGS AF: 0.669 AC: 2328 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.4
Dann	Benign	0.70

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: rs740949; hg19: chr7-148506064; COSMIC: COSV100234625; COSMIC: COSV100234625;