chr2-68218181-ATTAAT-A

Position:

• chr2-68218181-ATTAAT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000945.4(PPP3R1):​c.4-1055_4-1051del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,084 control chromosomes in the GnomAD database, including 1,263 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.11 (1263 hom., cov: 30)
• Consequence: PPP3R1 NM_000945.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.534

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.4-1055_4-1051del		intron_variant		ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.4-1055_4-1051del		intron_variant		1	NM_000945.4	P1
PPP3R1	ENST00000409377.1	c.-27-1055_-27-1051del		intron_variant		3
PPP3R1	ENST00000409752.5	c.61-1055_61-1051del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17154 AN: 151966 Hom.: 1257 Cov.: 30

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00672

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.113 AC: 17175 AN: 152084 Hom.: 1263 Cov.: 30 AF XY: 0.110 AC XY: 8149 AN XY: 74368

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0963

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.00674

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.127

Alfa AF: 0.100 Hom.: 117

Bravo AF: 0.119

Asia WGS AF: 0.113 AC: 391 AN: 3470

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Devine Lab Institute for Genome Sciences, University of Maryland School of Medicine

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3039851; hg19: chr2-68445313;