rs8080306
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000358598.6(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
ENST00000358598.6 5_prime_UTR
ENST00000358598.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.87
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]
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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=-0.72).
BP6
?
Variant 17-68512102-C-A is Benign according to our data. Variant chr17-68512102-C-A is described in ClinVar as [Benign]. Clinvar id is 1295447.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1A | NM_001369389.1 | c.-180C>A | 5_prime_UTR_variant | 1/12 | |||
PRKAR1A | NM_212471.3 | c.-47C>A | 5_prime_UTR_variant | 1/11 | |||
PRKAR1A | NM_001278433.2 | c.-6-3292C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000358598.6 | c.-47C>A | 5_prime_UTR_variant | 1/11 | 1 | P1 | |||
ENST00000590353.1 | n.174-3292C>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
PRKAR1A | ENST00000589017.6 | c.-180C>A | 5_prime_UTR_variant | 1/12 | 3 | P1 | |||
PRKAR1A | ENST00000592800.6 | c.-47C>A | 5_prime_UTR_variant | 1/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.730 AC: 110827AN: 151816Hom.: 40634 Cov.: 31
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GnomAD4 exome AF: 0.760 AC: 1714AN: 2256Hom.: 658 Cov.: 0 AF XY: 0.751 AC XY: 1217AN XY: 1620
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GnomAD4 genome ? AF: 0.730 AC: 110905AN: 151934Hom.: 40657 Cov.: 31 AF XY: 0.734 AC XY: 54494AN XY: 74266
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at