rs4671887

Positions:

• chr2-68248463-C-A

Variant summary

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

The NM_000945.4(PPP3R1):​c.3+3662G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,184 control chromosomes in the GnomAD database, including 43,218 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 0.74 (43218 hom., cov: 32)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.3+3662G>T		intron_variant		ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.3+3662G>T		intron_variant		1	NM_000945.4	P1
PPP3R1	ENST00000409377.1	c.-28+2528G>T		intron_variant		3
PPP3R1	ENST00000409752.5	c.60+7593G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113159 AN: 152066 Hom.: 43148 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.744 AC: 113286 AN: 152184 Hom.: 43218 Cov.: 32 AF XY: 0.743 AC XY: 55283 AN XY: 74404

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.736

Alfa AF: 0.701 Hom.: 4751

Bravo AF: 0.754

Asia WGS AF: 0.770 AC: 2676 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	9.7
DANN	Benign	0.64

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: rs4671887; hg19: chr2-68475595;