rs7480390

Positions:

• chr11-67402128-C-G

Variant summary

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

The ENST00000537694.2(PPP1CA):​n.187-929G>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CA	ENST00000537694.2	n.187-929G>C		intron_variant, non_coding_transcript_variant		5
PPP1CA	ENST00000542876.1	n.396-929G>C		intron_variant, non_coding_transcript_variant		3
PPP1CA	ENST00000546202.5	n.358-929G>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.0658

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0746

Gnomad4 OTH AF: 0.228

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7480390; hg19: chr11-67169599;