rs11158490

Variant names:

• chr14-63410452-T-G
• rs11158490
• NM_006246.5:c.549+4688A>C

Variant summary

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

The NM_006246.5(PPP2R5E):​c.549+4688A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,852 control chromosomes in the GnomAD database, including 9,230 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 0.28 (9230 hom., cov: 31)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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.549+4688A>C		intron	N/A	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.549+4688A>C		intron	N/A	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.549+4688A>C		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.549+4688A>C		intron	N/A	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.549+4688A>C		intron	N/A	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.935+4688A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42753 AN: 151732 Hom.: 9207 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.282 AC: 42817 AN: 151852 Hom.: 9230 Cov.: 31 AF XY: 0.276 AC XY: 20521 AN XY: 74234

African (AFR) AF: 0.603 AC: 24948 AN: 41358

American (AMR) AF: 0.144 AC: 2205 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3468

East Asian (EAS) AF: 0.137 AC: 707 AN: 5164

South Asian (SAS) AF: 0.123 AC: 591 AN: 4810

European-Finnish (FIN) AF: 0.217 AC: 2286 AN: 10546

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10970 AN: 67932

Other (OTH) AF: 0.221 AC: 465 AN: 2102

Alfa AF: 0.221 Hom.: 8345

Bravo AF: 0.290

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.65
PhyloP100		-0.38
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: rs11158490; hg19: chr14-63877170;