chr2-68180794-A-G

Position:

• chr2-68180794-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000945.4(PPP3R1):​c.*169T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 630,888 control chromosomes in the GnomAD database, including 40,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7776 hom., cov: 32)
  • Exomes 𝑓: 0.36 (33120 hom.)
• Consequence: PPP3R1 NM_000945.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.43

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 2-68180794-A-G is Benign according to our data. Variant chr2-68180794-A-G is described in ClinVar as [Benign]. Clinvar id is 1284063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3R1	NM_000945.4	c.*169T>C		3_prime_UTR_variant	6/6	ENST00000234310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3R1	ENST00000234310.8	c.*169T>C		3_prime_UTR_variant	6/6	1	NM_000945.4	P1
PPP3R1	ENST00000409752.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44894 AN: 151972 Hom.: 7780 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.358 AC: 171423 AN: 478798 Hom.: 33120 Cov.: 6 AF XY: 0.367 AC XY: 92928 AN XY: 253084

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.295 AC: 44893 AN: 152090 Hom.: 7776 Cov.: 32 AF XY: 0.308 AC XY: 22891 AN XY: 74324

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.318

Alfa AF: 0.265 Hom.: 1288

Bravo AF: 0.275

Asia WGS AF: 0.459 AC: 1592 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 30388516) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.89

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: rs875; hg19: chr2-68407926;