rs7960761

Positions:

• chr12-110726610-T-C

Variant summary

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

The NM_002710.4(PPP1CC):​c.419-1846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,076 control chromosomes in the GnomAD database, including 1,186 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 0.12 (1186 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: PPP1CC NM_002710.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1CC	NM_002710.4	c.419-1846A>G		intron_variant		ENST00000335007.10	NP_002701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1CC	ENST00000335007.10	c.419-1846A>G		intron_variant		1	NM_002710.4	ENSP00000335084	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17583 AN: 151924 Hom.: 1185 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.118 AC: 4 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 4 AN XY: 24

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.116 AC: 17601 AN: 152042 Hom.: 1186 Cov.: 32 AF XY: 0.113 AC XY: 8378 AN XY: 74334

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.0985

Gnomad4 OTH AF: 0.111

Alfa AF: 0.108 Hom.: 187

Bravo AF: 0.118

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.61

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: rs7960761; hg19: chr12-111164415;