14-63486804-C-T

Variant names:

• chr14-63486804-C-T
• rs11158493
• NM_006246.5:c.158-32919G>A

Variant summary

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

The NM_006246.5(PPP2R5E):​c.158-32919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,962 control chromosomes in the GnomAD database, including 12,568 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 0.35 (12568 hom., cov: 31)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006246.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.158-32919G>A		intron	N/A	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.158-32919G>A		intron	N/A	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.158-32919G>A		intron	N/A	NP_001269109.1	Q16537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.158-32919G>A		intron	N/A	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.158-32919G>A		intron	N/A	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.740+52725G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52905 AN: 151844 Hom.: 12524 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.349 AC: 53001 AN: 151962 Hom.: 12568 Cov.: 31 AF XY: 0.345 AC XY: 25623 AN XY: 74276

African (AFR) AF: 0.679 AC: 28124 AN: 41416

American (AMR) AF: 0.219 AC: 3344 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5164

South Asian (SAS) AF: 0.207 AC: 998 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2563 AN: 10546

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14532 AN: 67986

Other (OTH) AF: 0.327 AC: 691 AN: 2112

Alfa AF: 0.263 Hom.: 21197

Bravo AF: 0.360

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.19
PhyloP100		-0.35
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: rs11158493; hg19: chr14-63953522;