rs524

Positions:

• chr19-48875910-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014330.5(PPP1R15A):​c.1962C>T​(p.Ala654=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,613,100 control chromosomes in the GnomAD database, including 72,966 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 (10432 hom., cov: 33)
  • Exomes 𝑓: 0.29 (62534 hom.)
• Consequence: PPP1R15A NM_014330.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845

Genes affected

PPP1R15A (HGNC:14375): (protein phosphatase 1 regulatory subunit 15A) This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=0.845 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R15A	NM_014330.5	c.1962C>T	p.Ala654=	synonymous_variant	3/3	ENST00000200453.6	NP_055145.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R15A	ENST00000200453.6	c.1962C>T	p.Ala654=	synonymous_variant	3/3	1	NM_014330.5	ENSP00000200453	P2
PPP1R15A	ENST00000704027.1	c.2010C>T	p.Ala670=	synonymous_variant	2/2			ENSP00000515637	A2
PPP1R15A	ENST00000704026.1	c.1677C>T	p.Ala559=	synonymous_variant	4/4			ENSP00000515636	A2
PPP1R15A	ENST00000600406.2	c.*817C>T		3_prime_UTR_variant	2/2			ENSP00000469239

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53441 AN: 152032 Hom.: 10418 Cov.: 33

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.294 AC: 73739 AN: 250696 Hom.: 11533 AF XY: 0.294 AC XY: 39794 AN XY: 135552

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.327

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.287 AC: 419609 AN: 1460950 Hom.: 62534 Cov.: 35 AF XY: 0.288 AC XY: 209280 AN XY: 726680

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.352 AC: 53513 AN: 152150 Hom.: 10432 Cov.: 33 AF XY: 0.351 AC XY: 26116 AN XY: 74380

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.348

Alfa AF: 0.294 Hom.: 8331

Bravo AF: 0.356

Asia WGS AF: 0.275 AC: 954 AN: 3478

EpiCase AF: 0.281

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.5
DANN	Benign	0.74
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs524; hg19: chr19-49379167; COSMIC: COSV52338373;