Variant 7-550592-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001164760.2(PRKAR1B):c.984A>G(p.Ala328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,579,800 control chromosomes in the GnomAD database, including 885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 124 hom., cov: 32)

Exomes 𝑓: 0.010 ( 761 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:3

Conservation

PhyloP100: -3.64

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 7-550592-T-C is Benign according to our data. Variant chr7-550592-T-C is described in ClinVar as [Benign]. Clinvar id is 1210095.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-550592-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.984A>G	p.Ala328=	synonymous_variant	11/11	ENST00000537384.6	NP_001158232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.984A>G	p.Ala328=	synonymous_variant	11/11	5	NM_001164760.2	ENSP00000440449	P1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3358

AN:

151804

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00767

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00424

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0214

AC:

4460

AN:

208320

Hom.:

251

AF XY:

0.0201

AC XY:

2290

AN XY:

114066

show subpopulations

Gnomad AFR exome

AF:

0.0481

Gnomad AMR exome

AF:

0.00426

Gnomad ASJ exome

AF:

0.00342

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00138

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0101

AC:

14436

AN:

1427878

Hom.:

761

Cov.:

AF XY:

0.0102

AC XY:

7258

AN XY:

708444

show subpopulations

Gnomad4 AFR exome

AF:

0.0510

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.0144

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00290

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0222

AC:

3368

AN:

151922

Hom.:

124

Cov.:

AF XY:

0.0230

AC XY:

1712

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0486

Gnomad4 AMR

AF:

0.00759

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00424

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.0760

AC:

264

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

-0.92

CADD

Benign

0.086

DANN

Benign

0.45

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