rs351401

Positions:

• chr1-212290450-A-T

Variant summary

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

The NM_006243.4(PPP2R5A):​c.181+4159A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,116 control chromosomes in the GnomAD database, including 7,353 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 0.30 (7353 hom., cov: 32)
• Consequence: PPP2R5A NM_006243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

Genes affected

PPP2R5A (HGNC:9309): (protein phosphatase 2 regulatory subunit B'alpha) The product of 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 alpha isoform of the regulatory subunit B56 subfamily. Alternative transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R5A	NM_006243.4	c.181+4159A>T		intron_variant		ENST00000261461.7	NP_006234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R5A	ENST00000261461.7	c.181+4159A>T		intron_variant		1	NM_006243.4	ENSP00000261461	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45598 AN: 151998 Hom.: 7355 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.300 AC: 45607 AN: 152116 Hom.: 7353 Cov.: 32 AF XY: 0.296 AC XY: 22033 AN XY: 74354

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.326

Alfa AF: 0.326 Hom.: 1216

Bravo AF: 0.301

Asia WGS AF: 0.288 AC: 1001 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.82

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: rs351401; hg19: chr1-212463792;