NM_000945.4:c.3+3971G>A

Variant names:

• chr2-68248154-C-T
• rs6546365
• NM_000945.4:c.3+3971G>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.3+3971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,848 control chromosomes in the GnomAD database, including 15,995 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 0.46 (15995 hom., cov: 31)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 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.3+3971G>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.3+3971G>A		intron	N/A	ENSP00000234310.3	P63098
	ENSG00000273398	ENST00000406334.3	TSL:2	n.-28+4834G>A		intron	N/A	ENSP00000384974.3	H7BYZ3
	PPP3R1	ENST00000409752.5	TSL:3	c.60+7902G>A		intron	N/A	ENSP00000387216.1	D3YTA9

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69039 AN: 151728 Hom.: 15977 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.554

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: 0.455 AC: 69106 AN: 151848 Hom.: 15995 Cov.: 31 AF XY: 0.463 AC XY: 34374 AN XY: 74196

African (AFR) AF: 0.496 AC: 20512 AN: 41364

American (AMR) AF: 0.476 AC: 7257 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3466

East Asian (EAS) AF: 0.506 AC: 2616 AN: 5166

South Asian (SAS) AF: 0.619 AC: 2985 AN: 4820

European-Finnish (FIN) AF: 0.537 AC: 5648 AN: 10512

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27060 AN: 67950

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.429 Hom.: 1838

Bravo AF: 0.448

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.67
PhyloP100		-0.15
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: rs6546365; hg19: chr2-68475286;