rs12713636

chr2-68208299-C-G

Variant summary

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

The NM_000945.4(PPP3R1):c.43+8793G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,176 control chromosomes in the GnomAD database, including 43,316 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 0.75 (43316 hom., cov: 32)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

Genes affected

PPP3R1 (HGNC:9317): (protein phosphatase 3 regulatory subunit B, alpha) Enables cyclosporin A binding activity; phosphatase binding activity; and protein domain specific binding activity. Involved in calcineurin-NFAT signaling cascade and positive regulation of transcription by RNA polymerase II. Part of calcineurin complex. Implicated in Alzheimer's disease and dilated cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.43+8793G>C		intron_variant		ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.43+8793G>C		intron_variant		1	NM_000945.4	P1
PPP3R1	ENST00000409377.1	c.13+8793G>C		intron_variant		3
PPP3R1	ENST00000409752.5	c.100+8793G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113281 AN: 152058 Hom.: 43246 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.745 AC: 113408 AN: 152176 Hom.: 43316 Cov.: 32 AF XY: 0.744 AC XY: 55340 AN XY: 74396

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.737

Alfa AF: 0.702 Hom.: 4770

Bravo AF: 0.754

Asia WGS AF: 0.770 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	3.1
Dann	Benign	0.75

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: rs12713636; hg19: chr2-68435431;