rs7480390

Variant names:

• chr11-67402128-C-G
• rs7480390
• ENST00000537694.2:n.187-929G>C

Variant summary

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

The ENST00000537694.2(PPP1CA):​n.187-929G>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 152,196 control chromosomes in the GnomAD database, including 11,975 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 (11975 hom., cov: 33)
• Consequence: PPP1CA ENST00000537694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 6 publications found

Genes affected

PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CA	ENST00000537694.2	n.187-929G>C		intron_variant	Intron 1 of 6	5
PPP1CA	ENST00000542876.1	n.396-929G>C		intron_variant	Intron 2 of 3	3
PPP1CA	ENST00000546202.5	n.358-929G>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42775 AN: 152078 Hom.: 11932 Cov.: 33

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.282 AC: 42877 AN: 152196 Hom.: 11975 Cov.: 33 AF XY: 0.278 AC XY: 20724 AN XY: 74434

African (AFR) AF: 0.711 AC: 29513 AN: 41504

American (AMR) AF: 0.315 AC: 4818 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1201 AN: 5178

South Asian (SAS) AF: 0.0658 AC: 318 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1197 AN: 10618

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0746 AC: 5070 AN: 67996

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.185 Hom.: 859

Bravo AF: 0.322

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.065
DANN	Benign	0.41
PhyloP100		-0.14
PromoterAI		0.077	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7480390; hg19: chr11-67169599;