chr17-68512102-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_212471.3(PRKAR1A):c.-47C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 154,190 control chromosomes in the GnomAD database, including 41,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40657 hom., cov: 31)

Exomes 𝑓: 0.76 ( 658 hom. )

Consequence

PRKAR1A
NM_212471.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.87

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

Acrodysostosis 1 with or without hormone resistance
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
acrodysostosis with multiple hormone resistance
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
Carney complex, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
pigmented nodular adrenocortical disease, primary, 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
acrodysostosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Carney complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial atrial myxoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary pigmented nodular adrenocortical disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRKAR1A links:

ENSG00000267009 (HGNC:):

ENSG00000267009 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-68512102-C-A is Benign according to our data. Variant chr17-68512102-C-A is described in ClinVar as Benign. ClinVar VariationId is 1295447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212471.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKAR1A	NM_001369389.1	c.-180C>A	5_prime_UTR	Exon 1 of 12	NP_001356318.1	P10644-1
PRKAR1A	NM_212471.3	c.-47C>A	5_prime_UTR	Exon 1 of 11	NP_997636.1	P10644-1
PRKAR1A	NM_001278433.2	c.-6-3292C>A	intron	N/A	NP_001265362.1	B2R5T5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKAR1A	ENST00000358598.6	TSL:1	c.-47C>A	5_prime_UTR	Exon 1 of 11	ENSP00000351410.1	P10644-1
PRKAR1A	ENST00000589017.6	TSL:3	c.-180C>A	5_prime_UTR	Exon 1 of 12	ENSP00000465445.2	P10644-1
PRKAR1A	ENST00000592800.6	TSL:2	c.-47C>A	5_prime_UTR	Exon 1 of 10	ENSP00000466314.2	K7EM13

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110827

AN:

151816

Hom.:

40634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.695

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.767

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.959

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.761

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.751

GnomAD4 exome

AF:

0.760

AC:

1714

AN:

2256

Hom.:

658

Cov.:

AF XY:

0.751

AC XY:

1217

AN XY:

1620

show subpopulations

African (AFR)

AF:

0.625

AC:

AN:

American (AMR)

AF:

0.769

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.956

AC:

AN:

South Asian (SAS)

AF:

0.795

AC:

AN:

European-Finnish (FIN)

AF:

0.741

AC:

246

AN:

332

Middle Eastern (MID)

AF:

0.889

AC:

AN:

European-Non Finnish (NFE)

AF:

0.751

AC:

1179

AN:

1570

Other (OTH)

AF:

0.805

AC:

124

AN:

154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.730

AC:

110905

AN:

151934

Hom.:

40657

Cov.:

AF XY:

0.734

AC XY:

54494

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.694

AC:

28775

AN:

41440

American (AMR)

AF:

0.767

AC:

11719

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2481

AN:

3472

East Asian (EAS)

AF:

0.959

AC:

4929

AN:

5140

South Asian (SAS)

AF:

0.776

AC:

3741

AN:

4820

European-Finnish (FIN)

AF:

0.761

AC:

8046

AN:

10570

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.718

AC:

48726

AN:

67896

Other (OTH)

AF:

0.750

AC:

1583

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1498

2997

4495

5994

7492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.725

Hom.:

96795

Bravo

AF:

0.730

Asia WGS

AF:

0.862

AC:

2998

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.1

(source)

DANN

Benign

0.75

PhyloP100

-1.9

PromoterAI

-0.057

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.3

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over