2-68248154-C-T

Position:

• chr2-68248154-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.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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3R1	NM_000945.4	c.3+3971G>A		intron_variant		ENST00000234310.8	NP_000936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3R1	ENST00000234310.8	c.3+3971G>A		intron_variant		1	NM_000945.4	ENSP00000234310.3
ENSG00000273398	ENST00000406334.3	n.-28+4834G>A		intron_variant		2		ENSP00000384974.3
PPP3R1	ENST00000409752.5	c.60+7902G>A		intron_variant		3		ENSP00000387216.1
PPP3R1	ENST00000409377.1	c.-28+2837G>A		intron_variant		3		ENSP00000387148.1

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

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.477

Alfa AF: 0.425 Hom.: 1751

Bravo AF: 0.448

Asia WGS AF: 0.587 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.67

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: rs6546365; hg19: chr2-68475286;