chr2-68181905-G-A

Variant names:

• chr2-68181905-G-A
• rs1868402
• NM_000945.4:c.466-895C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000945.4(PPP3R1):​c.466-895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,150 control chromosomes in the GnomAD database, including 47,609 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 0.78 (47609 hom., cov: 31)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 26 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3R1	NM_000945.4	MANE Select	c.466-895C>T		intron	N/A	NP_000936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3R1	ENST00000234310.8	TSL:1 MANE Select	c.466-895C>T		intron	N/A	ENSP00000234310.3
	ENSG00000273398	ENST00000406334.3	TSL:2	n.435+4563C>T		intron	N/A	ENSP00000384974.3
	PPP3R1	ENST00000409752.5	TSL:3	c.523-895C>T		intron	N/A	ENSP00000387216.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119176 AN: 152032 Hom.: 47545 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.784 AC: 119301 AN: 152150 Hom.: 47609 Cov.: 31 AF XY: 0.782 AC XY: 58197 AN XY: 74380

African (AFR) AF: 0.943 AC: 39160 AN: 41524

American (AMR) AF: 0.764 AC: 11689 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2740 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3257 AN: 5178

South Asian (SAS) AF: 0.827 AC: 3991 AN: 4828

European-Finnish (FIN) AF: 0.722 AC: 7607 AN: 10540

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48218 AN: 67988

Other (OTH) AF: 0.784 AC: 1658 AN: 2116

Alfa AF: 0.727 Hom.: 32796

Bravo AF: 0.790

Asia WGS AF: 0.783 AC: 2722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-0.95
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: rs1868402; hg19: chr2-68409037;