7-550562-A-G
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1
The NM_001164760.2(PRKAR1B):āc.1014T>Cā(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 (no stars).
Frequency
Genomes: š 0.15 ( 1813 hom., cov: 32)
Exomes š: 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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 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 no_assertion_criteria_provided, 0 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
GnomAD3 genomes
AF:
AC:
22447
AN:
151996
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.132 AC: 30002AN: 228116Hom.: 2226 AF XY: 0.126 AC XY: 15737AN XY: 124968
GnomAD3 exomes
AF:
AC:
30002
AN:
228116
Hom.:
AF XY:
AC XY:
15737
AN XY:
124968
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.127 AC: 183052AN: 1446278Hom.: 12408 Cov.: 32 AF XY: 0.124 AC XY: 89057AN XY: 718754
GnomAD4 exome
AF:
AC:
183052
AN:
1446278
Hom.:
Cov.:
32
AF XY:
AC XY:
89057
AN XY:
718754
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.148 AC: 22478AN: 152114Hom.: 1813 Cov.: 32 AF XY: 0.146 AC XY: 10889AN XY: 74350
GnomAD4 genome
AF:
AC:
22478
AN:
152114
Hom.:
Cov.:
32
AF XY:
AC XY:
10889
AN XY:
74350
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
501
AN:
3478
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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at