19-48873985-G-C

Variant names:

• chr19-48873985-G-C
• rs557806
• NM_014330.5:c.752G>C

Variant summary

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

The NM_014330.5(PPP1R15A):​c.752G>C​(p.Arg251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,804 control chromosomes in the GnomAD database, including 35,810 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (10793 hom., cov: 32)
  • Exomes 𝑓: 0.16 (25017 hom.)
• Consequence: PPP1R15A NM_014330.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 31 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.8412487E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014330.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R15A	NM_014330.5	MANE Select	c.752G>C	p.Arg251Pro	missense	Exon 2 of 3	NP_055145.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R15A	ENST00000200453.6	TSL:1 MANE Select	c.752G>C	p.Arg251Pro	missense	Exon 2 of 3	ENSP00000200453.4
	PPP1R15A	ENST00000704027.1		c.800G>C	p.Arg267Pro	missense	Exon 1 of 2	ENSP00000515637.1
	PPP1R15A	ENST00000600406.2	TSL:6	c.752G>C	p.Arg251Pro	missense	Exon 2 of 2	ENSP00000469239.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45187 AN: 151916 Hom.: 10751 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.202 AC: 50833 AN: 251148 AF XY: 0.195

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.159 AC: 232924 AN: 1461770 Hom.: 25017 Cov.: 37 AF XY: 0.161 AC XY: 116847 AN XY: 727176

African (AFR) AF: 0.685 AC: 22913 AN: 33474

American (AMR) AF: 0.217 AC: 9711 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5181 AN: 26128

East Asian (EAS) AF: 0.108 AC: 4293 AN: 39698

South Asian (SAS) AF: 0.262 AC: 22585 AN: 86252

European-Finnish (FIN) AF: 0.169 AC: 9023 AN: 53416

Middle Eastern (MID) AF: 0.219 AC: 1263 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 146552 AN: 1111938

Other (OTH) AF: 0.189 AC: 11403 AN: 60386

GnomAD4 genome AF: 0.298 AC: 45291 AN: 152034 Hom.: 10793 Cov.: 32 AF XY: 0.297 AC XY: 22115 AN XY: 74340

African (AFR) AF: 0.662 AC: 27412 AN: 41410

American (AMR) AF: 0.241 AC: 3683 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3466

East Asian (EAS) AF: 0.107 AC: 555 AN: 5174

South Asian (SAS) AF: 0.285 AC: 1375 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9080 AN: 67986

Other (OTH) AF: 0.294 AC: 620 AN: 2106

Alfa AF: 0.136 Hom.: 1382

Bravo AF: 0.317

TwinsUK AF: 0.136 AC: 504

ALSPAC AF: 0.133 AC: 513

ESP6500AA AF: 0.657 AC: 2894

ESP6500EA AF: 0.133 AC: 1142

ExAC AF: 0.210 AC: 25551

Asia WGS AF: 0.237 AC: 821 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.43
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.20
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.046
Sift	Benign	0.47	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.12
ClinPred		0.0045	T
GERP RS		1.2
PromoterAI		-0.0012	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.23
gMVP		0.093
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: rs557806; hg19: chr19-49377242; COSMIC: COSV52338692; COSMIC: COSV52338692;