Variant chr7-550511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_001164760.2(PRKAR1B):c.1065C>T(p.Phe355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,603,114 control chromosomes in the GnomAD database, including 827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 92 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 735 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:3

Conservation

PhyloP100: -0.440

Variant links:

Genes affected

PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]

PRKAR1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 7-550511-G-A is Benign according to our data. Variant chr7-550511-G-A is described in ClinVar as [Benign]. Clinvar id is 1210096.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-550511-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.1065C>T	p.Phe355=	synonymous_variant	11/11	ENST00000537384.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.1065C>T	p.Phe355=	synonymous_variant	11/11	5	NM_001164760.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2530

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00421

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0194

AC:

4412

AN:

227768

Hom.:

256

AF XY:

0.0186

AC XY:

2295

AN XY:

123608

show subpopulations

Gnomad AFR exome

AF:

0.0302

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.00306

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00151

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.00958

AC:

13898

AN:

1450876

Hom.:

735

Cov.:

AF XY:

0.00982

AC XY:

7079

AN XY:

720660

show subpopulations

Gnomad4 AFR exome

AF:

0.0301

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.0145

Gnomad4 FIN exome

AF:

0.00158

Gnomad4 NFE exome

AF:

0.00294

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0167

AC:

2535

AN:

152238

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1307

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00421

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00893

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

PRKAR1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

1.7

DANN

Benign

0.87

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