Variant 7-550568-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164760.2(PRKAR1B):c.1008G>A(p.Ala336=) 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

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]

PRKAR1B links:

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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=-0.58).

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.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00142 (216/152168) while in subpopulation NFE AF= 0.00119 (81/67968). AF 95% confidence interval is 0.000982. There are 2 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.1008G>A	p.Ala336=	synonymous_variant	11/11	ENST00000537384.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.1008G>A	p.Ala336=	synonymous_variant	11/11	5	NM_001164760.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152050

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.000684

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 13, 2018

- -

PRKAR1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2024

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over