rs12713636

Variant names:

• chr2-68208299-C-G
• rs12713636
• NM_000945.4:c.43+8793G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000273398 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP3R1	NM_000945.4	c.43+8793G>C		intron_variant	Intron 2 of 5	ENST00000234310.8	NP_000936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3R1	ENST00000234310.8	c.43+8793G>C		intron_variant	Intron 2 of 5	1	NM_000945.4	ENSP00000234310.3
ENSG00000273398	ENST00000406334.3	n.13+8793G>C		intron_variant	Intron 3 of 14	2		ENSP00000384974.3
PPP3R1	ENST00000409752.5	c.100+8793G>C		intron_variant	Intron 2 of 5	3		ENSP00000387216.1
PPP3R1	ENST00000409377.1	c.13+8793G>C		intron_variant	Intron 2 of 5	3		ENSP00000387148.1

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

African (AFR) AF: 0.932 AC: 38737 AN: 41560

American (AMR) AF: 0.721 AC: 11030 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2479 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3373 AN: 5178

South Asian (SAS) AF: 0.778 AC: 3750 AN: 4820

European-Finnish (FIN) AF: 0.685 AC: 7235 AN: 10562

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44340 AN: 67974

Other (OTH) AF: 0.737 AC: 1556 AN: 2112

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
PhyloP100		-0.065
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: rs12713636; hg19: chr2-68435431;