Variant chr2-68188635-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000945.4(PPP3R1):c.99C>T(p.Asp33=) variant causes a synonymous change. The variant allele was found at a frequency of 0.429 in 1,611,810 control chromosomes in the GnomAD database, including 152,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16010 hom., cov: 31)

Exomes 𝑓: 0.43 ( 136001 hom. )

Consequence

PPP3R1
NM_000945.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.12

Variant links:

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]

PPP3R1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-68188635-G-A is Benign according to our data. Variant chr2-68188635-G-A is described in ClinVar as [Benign]. Clinvar id is 1181494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3R1	NM_000945.4 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	3/6	ENST00000234310.8	NP_000936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PPP3R1	ENST00000234310.8 linkuse as main transcript	c.99C>T	p.Asp33=	synonymous_variant	3/6	1	NM_000945.4	ENSP00000234310	P1
PPP3R1	ENST00000409752.5 linkuse as main transcript	c.156C>T	p.Asp52=	synonymous_variant	3/6	3		ENSP00000387216
PPP3R1	ENST00000409377.1 linkuse as main transcript	c.69C>T	p.Asp23=	synonymous_variant	3/6	3		ENSP00000387148

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69109

AN:

151774

Hom.:

15994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.473

GnomAD3 exomes

AF:

0.473

AC:

117015

AN:

247438

Hom.:

28599

AF XY:

0.480

AC XY:

64440

AN XY:

134372

show subpopulations

Gnomad AFR exome

AF:

0.493

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.514

Gnomad SAS exome

AF:

0.635

Gnomad FIN exome

AF:

0.538

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.426

AC:

621984

AN:

1459918

Hom.:

136001

Cov.:

AF XY:

0.432

AC XY:

314112

AN XY:

726282

show subpopulations

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.632

Gnomad4 FIN exome

AF:

0.535

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.455

AC:

69174

AN:

151892

Hom.:

16010

Cov.:

AF XY:

0.464

AC XY:

34425

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.492

Gnomad4 AMR

AF:

0.477

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.421

Hom.:

8959

Bravo

AF:

0.447

Asia WGS

AF:

0.586

AC:

2032

AN:

3472

EpiCase

AF:

0.418

EpiControl

AF:

0.411

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jun 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over