rs1822469

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-68227553-C-A
• chr2-68227553-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000945.4(PPP3R1):​c.4-10422G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.4-10422G>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.4-10422G>T		intron	N/A	ENSP00000234310.3
	ENSG00000273398	ENST00000406334.3	TSL:2	n.-27-10422G>T		intron	N/A	ENSP00000384974.3
	PPP3R1	ENST00000409752.5	TSL:3	c.61-10422G>T		intron	N/A	ENSP00000387216.1

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 1965

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		0.12

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;