rs4147456

Variant names:

• chr14-63434014-C-T
• rs4147456
• NM_006246.5:c.355-11920G>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.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
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 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.355-11920G>A		intron	N/A	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.355-11920G>A		intron	N/A	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.355-11920G>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.355-11920G>A		intron	N/A	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.355-11920G>A		intron	N/A	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.741-11920G>A		intron	N/A

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

African (AFR) AF: 0.435 AC: 18026 AN: 41418

American (AMR) AF: 0.125 AC: 1907 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 484 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5174

South Asian (SAS) AF: 0.110 AC: 532 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1311 AN: 10564

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8176 AN: 67982

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.165 Hom.: 4299

Bravo AF: 0.218

Asia WGS AF: 0.179 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.17
PhyloP100		-0.34
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: rs4147456; hg19: chr14-63900732;