7-148808368-G-C

Position:

• chr7-148808368-G-C

Variant summary

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

The ENST00000320356.7(EZH2):​c.2196-662C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,190 control chromosomes in the GnomAD database, including 33,209 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 0.66 (33209 hom., cov: 34)
• Consequence: EZH2 ENST00000320356.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EZH2	NM_004456.5	c.2196-662C>G		intron_variant		ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7	c.2196-662C>G		intron_variant		1	NM_004456.5	ENSP00000320147	P4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99812 AN: 152070 Hom.: 33185 Cov.: 34

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.656 AC: 99892 AN: 152190 Hom.: 33209 Cov.: 34 AF XY: 0.654 AC XY: 48636 AN XY: 74376

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.637

Alfa AF: 0.629 Hom.: 3766

Bravo AF: 0.672

Asia WGS AF: 0.655 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.43

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: rs734004; hg19: chr7-148505460;