7-148846601-TAAA-TAAAA

Position:

• chr7-148846601-TAAA-TAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004456.5(EZH2):​c.118-4_118-3insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00072 (0 hom.)
• Consequence: EZH2 NM_004456.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476

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 -10 ACMG points.

• BP6: Variant 7-148846601-T-TA is Benign according to our data. Variant chr7-148846601-T-TA is described in ClinVar as [Benign]. Clinvar id is 2193760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000106 (16/150502) while in subpopulation SAS AF= 0.00126 (6/4754). AF 95% confidence interval is 0.000549. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EZH2	NM_004456.5	c.118-4_118-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320356.7	NP_004447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EZH2	ENST00000320356.7	c.118-4_118-3insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004456.5	ENSP00000320147	P4

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 150384 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000721 AC: 943 AN: 1307800 Hom.: 0 Cov.: 0 AF XY: 0.000753 AC XY: 490 AN XY: 651090

Gnomad4 AFR exome AF: 0.000106

Gnomad4 AMR exome AF: 0.00102

Gnomad4 ASJ exome AF: 0.000559

Gnomad4 EAS exome AF: 0.000585

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.000996

Gnomad4 NFE exome AF: 0.000663

Gnomad4 OTH exome AF: 0.000819

GnomAD4 genome AF: 0.000106 AC: 16 AN: 150502 Hom.: 0 Cov.: 0 AF XY: 0.000109 AC XY: 8 AN XY: 73408

Gnomad4 AFR AF: 0.0000730

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Weaver syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3214332; hg19: chr7-148543693;