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GeneBe

7-551465-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001164760.2(PRKAR1B):c.897C>T(p.Thr299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,553,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.01
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-551465-G-A is Benign according to our data. Variant chr7-551465-G-A is described in ClinVar as [Benign]. Clinvar id is 716001.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.01 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00107 (163/152234) while in subpopulation AFR AF= 0.00224 (93/41514). AF 95% confidence interval is 0.00187. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 163 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKAR1BNM_001164760.2 linkuse as main transcriptc.897C>T p.Thr299= synonymous_variant 10/11 ENST00000537384.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAR1BENST00000537384.6 linkuse as main transcriptc.897C>T p.Thr299= synonymous_variant 10/115 NM_001164760.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00107
AC:
163
AN:
152116
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00225
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000691
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000793
AC:
123
AN:
155048
Hom.:
0
AF XY:
0.000738
AC XY:
61
AN XY:
82662
show subpopulations
Gnomad AFR exome
AF:
0.00257
Gnomad AMR exome
AF:
0.00138
Gnomad ASJ exome
AF:
0.000120
Gnomad EAS exome
AF:
0.000581
Gnomad SAS exome
AF:
0.000607
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000654
Gnomad OTH exome
AF:
0.00138
GnomAD4 exome
AF:
0.000656
AC:
920
AN:
1401530
Hom.:
0
Cov.:
31
AF XY:
0.000648
AC XY:
448
AN XY:
691576
show subpopulations
Gnomad4 AFR exome
AF:
0.00167
Gnomad4 AMR exome
AF:
0.00151
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000434
Gnomad4 SAS exome
AF:
0.000703
Gnomad4 FIN exome
AF:
0.0000208
Gnomad4 NFE exome
AF:
0.000642
Gnomad4 OTH exome
AF:
0.000758
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00107
AC:
163
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.000927
AC XY:
69
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00224
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000691
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000722
Hom.:
0
Bravo
AF:
0.00125
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 submitterclinical testingInvitaeJan 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
0.049
Dann
Benign
0.90

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: rs76036113; hg19: chr7-591102; API