2-68227553-C-T

Variant names:

• chr2-68227553-C-T
• rs1822469
• NM_000945.4:c.4-10422G>A

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000945.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3R1	NM_000945.4	MANE Select	c.4-10422G>A		intron	N/A	NP_000936.1	P63098

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3R1	ENST00000234310.8	TSL:1 MANE Select	c.4-10422G>A		intron	N/A	ENSP00000234310.3	P63098
	ENSG00000273398	ENST00000406334.3	TSL:2	n.-27-10422G>A		intron	N/A	ENSP00000384974.3	H7BYZ3
	PPP3R1	ENST00000409752.5	TSL:3	c.61-10422G>A		intron	N/A	ENSP00000387216.1	D3YTA9

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

African (AFR) AF: 0.492 AC: 20249 AN: 41162

American (AMR) AF: 0.475 AC: 7211 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1596 AN: 3462

East Asian (EAS) AF: 0.506 AC: 2609 AN: 5156

South Asian (SAS) AF: 0.621 AC: 2975 AN: 4792

European-Finnish (FIN) AF: 0.537 AC: 5565 AN: 10372

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 26937 AN: 67640

Other (OTH) AF: 0.477 AC: 998 AN: 2092

Alfa AF: 0.355 Hom.: 1965

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.12
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: rs1822469; hg19: chr2-68454685;