Variant rs3785905 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000589228.6(PRKAR1A):c.709-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 523,032 control chromosomes in the GnomAD database, including 5,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1707 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4042 hom. )

Consequence

PRKAR1A
ENST00000589228.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.214

Variant links:

Genes affected

PRKAR1A (HGNC:9388): (protein kinase cAMP-dependent type I regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]

PRKAR1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-68527631-G-A is Benign according to our data. Variant chr17-68527631-G-A is described in ClinVar as [Benign]. Clinvar id is 677028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAR1A	NM_002734.5 linkuse as main transcript	c.709-209G>A		intron_variant		ENST00000589228.6	NP_002725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAR1A	ENST00000589228.6 linkuse as main transcript	c.709-209G>A		intron_variant		1	NM_002734.5	ENSP00000464977	P1	P10644-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22381

AN:

151738

Hom.:

1706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.144

AC:

53392

AN:

371174

Hom.:

4042

Cov.:

AF XY:

0.147

AC XY:

29188

AN XY:

198102

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.147

AC:

22384

AN:

151858

Hom.:

1707

Cov.:

AF XY:

0.148

AC XY:

10944

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.136

Hom.:

2917

Bravo

AF:

0.154

Asia WGS

AF:

0.189

AC:

656

AN:

3478

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 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.90

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