rs8009130

Positions:

• chr14-63511643-A-T

Variant summary

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

The NM_006246.5(PPP2R5E):​c.157+27886T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,284 control chromosomes in the GnomAD database, including 972 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 0.11 (972 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R5E	NM_006246.5	c.157+27886T>A		intron_variant		ENST00000337537.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.157+27886T>A		intron_variant		1	NM_006246.5	P1
PPP2R5E	ENST00000555899.1	c.157+27886T>A		intron_variant		1
PPP2R5E	ENST00000553266.5	n.740+27886T>A		intron_variant, non_coding_transcript_variant		1
PPP2R5E	ENST00000556878.1	n.759+27886T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16038 AN: 152166 Hom.: 970 Cov.: 32

Gnomad AFR AF: 0.0739

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.105 AC: 16037 AN: 152284 Hom.: 972 Cov.: 32 AF XY: 0.105 AC XY: 7828 AN XY: 74472

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.124 Hom.: 149

Bravo AF: 0.0976

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.74

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: rs8009130; hg19: chr14-63978361;