rs4147456

chr14-63434014-C-T

Variant summary

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

The NM_006246.5(PPP2R5E):c.355-11920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,012 control chromosomes in the GnomAD database, including 4,898 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 0.21 (4898 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

Genes affected

PPP2R5E (HGNC:9313): (protein phosphatase 2 regulatory subunit B'epsilon) The protein encoded by this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an epsilon isoform of the regulatory subunit B56 subfamily. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5E	NM_006246.5	c.355-11920G>A		intron_variant		ENST00000337537.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.355-11920G>A		intron_variant		1	NM_006246.5	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32049 AN: 151894 Hom.: 4881 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.211 AC: 32101 AN: 152012 Hom.: 4898 Cov.: 32 AF XY: 0.207 AC XY: 15393 AN XY: 74304

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.171

Alfa AF: 0.188 Hom.: 477

Bravo AF: 0.218

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.37
Dann	Benign	0.17

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: rs4147456; hg19: chr14-63900732;