7-550562-A-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001164760.2(PRKAR1B):c.1014T>C(p.Thr338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,598,392 control chromosomes in the GnomAD database, including 14,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.15 ( 1813 hom., cov: 32)
Exomes 𝑓: 0.13 ( 12408 hom. )
Consequence
PRKAR1B
NM_001164760.2 synonymous
NM_001164760.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.12
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 7-550562-A-G is Benign according to our data. Variant chr7-550562-A-G is described in ClinVar as [Benign]. Clinvar id is 1210100.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-550562-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.12 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1B | NM_001164760.2 | c.1014T>C | p.Thr338= | synonymous_variant | 11/11 | ENST00000537384.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1B | ENST00000537384.6 | c.1014T>C | p.Thr338= | synonymous_variant | 11/11 | 5 | NM_001164760.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.148 AC: 22447AN: 151996Hom.: 1814 Cov.: 32
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GnomAD3 exomes AF: 0.132 AC: 30002AN: 228116Hom.: 2226 AF XY: 0.126 AC XY: 15737AN XY: 124968
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GnomAD4 exome AF: 0.127 AC: 183052AN: 1446278Hom.: 12408 Cov.: 32 AF XY: 0.124 AC XY: 89057AN XY: 718754
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GnomAD4 genome ? AF: 0.148 AC: 22478AN: 152114Hom.: 1813 Cov.: 32 AF XY: 0.146 AC XY: 10889AN XY: 74350
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
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, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 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
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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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