Variant 7-550562-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001164760.2(PRKAR1B):c.1014T>C(p.Thr338Thr) 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: 𝑓 0.15 ( 1813 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12408 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

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]

PRKAR1B links:

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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 rank	MANE	Protein	UniProt
PRKAR1B	NM_001164760.2 link	c.1014T>C	p.Thr338Thr	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
PRKAR1B	ENST00000537384.6 link	c.1014T>C	p.Thr338Thr	synonymous_variant	Exon 11 of 11	5	NM_001164760.2	ENSP00000440449.1		P31321

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22447

AN:

151996

Hom.:

1814

Cov.:

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.:

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.:

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

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PRKAR1B-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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: 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.

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