rs17171119

Variant names:

• chr7-148820364-T-G
• rs17171119
• NM_004456.5:c.908-677A>C

Variant summary

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

The NM_004456.5(EZH2):​c.908-677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,178 control chromosomes in the GnomAD database, including 1,532 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 0.14 (1532 hom., cov: 32)
• Consequence: EZH2 NM_004456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZH2	NM_004456.5	c.908-677A>C		intron_variant	Intron 8 of 19	ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7	c.908-677A>C		intron_variant	Intron 8 of 19	1	NM_004456.5	ENSP00000320147.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20565 AN: 152060 Hom.: 1531 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.135 AC: 20567 AN: 152178 Hom.: 1532 Cov.: 32 AF XY: 0.139 AC XY: 10328 AN XY: 74412

African (AFR) AF: 0.0946 AC: 3931 AN: 41538

American (AMR) AF: 0.203 AC: 3096 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1329 AN: 5184

South Asian (SAS) AF: 0.182 AC: 878 AN: 4824

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9051 AN: 67988

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.139 Hom.: 553

Bravo AF: 0.142

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.39
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17171119; hg19: chr7-148517456;