7-550568-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001164760.2(PRKAR1B):​c.1008G>A​(p.Ala336Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,593,558 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.08
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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 7-550568-C-T is Benign according to our data. Variant chr7-550568-C-T is described in ClinVar as [Benign]. Clinvar id is 786768.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-550568-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-4.08 with no splicing effect.
BS2
High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKAR1BNM_001164760.2 linkc.1008G>A p.Ala336Ala synonymous_variant Exon 11 of 11 ENST00000537384.6 NP_001158232.1 P31321

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKAR1BENST00000537384.6 linkc.1008G>A p.Ala336Ala synonymous_variant Exon 11 of 11 5 NM_001164760.2 ENSP00000440449.1 P31321

Frequencies

GnomAD3 genomes
AF:
0.00142
AC:
216
AN:
152050
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000388
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0106
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00119
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00158
AC:
353
AN:
223822
Hom.:
0
AF XY:
0.00152
AC XY:
187
AN XY:
122938
show subpopulations
Gnomad AFR exome
AF:
0.000434
Gnomad AMR exome
AF:
0.000756
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000176
Gnomad SAS exome
AF:
0.0000357
Gnomad FIN exome
AF:
0.00804
Gnomad NFE exome
AF:
0.00157
Gnomad OTH exome
AF:
0.000942
GnomAD4 exome
AF:
0.00141
AC:
2039
AN:
1441390
Hom.:
4
Cov.:
32
AF XY:
0.00136
AC XY:
975
AN XY:
716018
show subpopulations
Gnomad4 AFR exome
AF:
0.000523
Gnomad4 AMR exome
AF:
0.000661
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000228
Gnomad4 SAS exome
AF:
0.0000595
Gnomad4 FIN exome
AF:
0.00880
Gnomad4 NFE exome
AF:
0.00133
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
AF:
0.00142
AC:
216
AN:
152168
Hom.:
2
Cov.:
32
AF XY:
0.00184
AC XY:
137
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000389
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0106
Gnomad4 NFE
AF:
0.00119
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000697
Hom.:
1
Bravo
AF:
0.000684
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 13, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

PRKAR1B-related disorder Benign:1
May 14, 2024
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely 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
-0.58
CADD
Benign
4.4
DANN
Benign
0.79

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: rs370829885; hg19: chr7-590205; COSMIC: COSV64319199; API