2-68227553-C-T

Position:

• chr2-68227553-C-T

Variant summary

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

The NM_000945.4(PPP3R1):​c.4-10422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,064 control chromosomes in the GnomAD database, including 15,806 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 0.45 (15806 hom., cov: 29)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.4-10422G>A		intron_variant		ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.4-10422G>A		intron_variant		1	NM_000945.4	P1
PPP3R1	ENST00000409377.1	c.-27-10422G>A		intron_variant		3
PPP3R1	ENST00000409752.5	c.61-10422G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68508 AN: 150950 Hom.: 15790 Cov.: 29

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.454 AC: 68570 AN: 151064 Hom.: 15806 Cov.: 29 AF XY: 0.462 AC XY: 34096 AN XY: 73786

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.477

Alfa AF: 0.345 Hom.: 1711

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.60

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: rs1822469; hg19: chr2-68454685;