Variant chr17-68530175-A-T 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.974-102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,514,986 control chromosomes in the GnomAD database, including 37,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3008 hom., cov: 32)

Exomes 𝑓: 0.22 ( 34357 hom. )

Consequence

PRKAR1A
ENST00000589228.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.144

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:

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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 17-68530175-A-T is Benign according to our data. Variant chr17-68530175-A-T is described in ClinVar as [Benign]. Clinvar id is 1229416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 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.974-102A>T		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.974-102A>T		intron_variant		1	NM_002734.5	ENSP00000464977	P1	P10644-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29419

AN:

151970

Hom.:

3010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.221

AC:

301429

AN:

1362898

Hom.:

34357

Cov.:

AF XY:

0.223

AC XY:

152544

AN XY:

683070

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.193

AC:

29413

AN:

152088

Hom.:

3008

Cov.:

AF XY:

0.194

AC XY:

14409

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.212

Hom.:

445

Bravo

AF:

0.183

Asia WGS

AF:

0.185

AC:

646

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	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

DANN

Benign

0.47

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