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):ā€‹c.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

Scores

2

Clinical Significance

Benign no assertion criteria provided B:3

Conservation

PhyloP100: -2.12
Variant links:
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 -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
PRKAR1BNM_001164760.2 linkuse as main transcriptc.1014T>C p.Thr338= synonymous_variant 11/11 ENST00000537384.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAR1BENST00000537384.6 linkuse as main transcriptc.1014T>C p.Thr338= synonymous_variant 11/115 NM_001164760.2 P1

Frequencies

GnomAD3 genomes
AF:
0.148
AC:
22447
AN:
151996
Hom.:
1814
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.211
Gnomad AMI
AF:
0.163
Gnomad AMR
AF:
0.103
Gnomad ASJ
AF:
0.0945
Gnomad EAS
AF:
0.230
Gnomad SAS
AF:
0.0696
Gnomad FIN
AF:
0.157
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.121
Gnomad OTH
AF:
0.130
GnomAD3 exomes
AF:
0.132
AC:
30002
AN:
228116
Hom.:
2226
AF XY:
0.126
AC XY:
15737
AN XY:
124968
show subpopulations
Gnomad AFR exome
AF:
0.218
Gnomad AMR exome
AF:
0.105
Gnomad ASJ exome
AF:
0.0881
Gnomad EAS exome
AF:
0.238
Gnomad SAS exome
AF:
0.0696
Gnomad FIN exome
AF:
0.171
Gnomad NFE exome
AF:
0.124
Gnomad OTH exome
AF:
0.124
GnomAD4 exome
AF:
0.127
AC:
183052
AN:
1446278
Hom.:
12408
Cov.:
32
AF XY:
0.124
AC XY:
89057
AN XY:
718754
show subpopulations
Gnomad4 AFR exome
AF:
0.215
Gnomad4 AMR exome
AF:
0.103
Gnomad4 ASJ exome
AF:
0.0890
Gnomad4 EAS exome
AF:
0.253
Gnomad4 SAS exome
AF:
0.0663
Gnomad4 FIN exome
AF:
0.168
Gnomad4 NFE exome
AF:
0.124
Gnomad4 OTH exome
AF:
0.123
GnomAD4 genome
AF:
0.148
AC:
22478
AN:
152114
Hom.:
1813
Cov.:
32
AF XY:
0.146
AC XY:
10889
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.211
Gnomad4 AMR
AF:
0.103
Gnomad4 ASJ
AF:
0.0945
Gnomad4 EAS
AF:
0.230
Gnomad4 SAS
AF:
0.0689
Gnomad4 FIN
AF:
0.157
Gnomad4 NFE
AF:
0.121
Gnomad4 OTH
AF:
0.128
Alfa
AF:
0.125
Hom.:
408
Bravo
AF:
0.148
Asia WGS
AF:
0.144
AC:
501
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
PRKAR1B-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 05, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.021
DANN
Benign
0.46

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.

Other links and lift over

dbSNP: rs11545042; hg19: chr7-590199; COSMIC: COSV64318316; API