rs1868402

Positions:

• chr2-68181905-G-A
• chr2-68181905-G-C
• chr2-68181905-G-T

Variant summary

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

The NM_000945.4(PPP3R1):​c.466-895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,150 control chromosomes in the GnomAD database, including 47,609 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 0.78 (47609 hom., cov: 31)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3R1	NM_000945.4	c.466-895C>T		intron_variant		ENST00000234310.8	NP_000936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3R1	ENST00000234310.8	c.466-895C>T		intron_variant		1	NM_000945.4	ENSP00000234310.3
ENSG00000273398	ENST00000406334.3	n.435+4563C>T		intron_variant		2		ENSP00000384974.3
PPP3R1	ENST00000409752.5	c.523-895C>T		intron_variant		3		ENSP00000387216.1
PPP3R1	ENST00000409377.1	c.436-895C>T		intron_variant		3		ENSP00000387148.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119176 AN: 152032 Hom.: 47545 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.784 AC: 119301 AN: 152150 Hom.: 47609 Cov.: 31 AF XY: 0.782 AC XY: 58197 AN XY: 74380

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.784

Alfa AF: 0.720 Hom.: 18025

Bravo AF: 0.790

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.31

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: rs1868402; hg19: chr2-68409037;