Variant 7-551429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001164760.2(PRKAR1B):c.933G>A(p.Glu311=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,560,526 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 10 hom. )

Consequence

PRKAR1B
NM_001164760.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.989

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 7-551429-C-T is Benign according to our data. Variant chr7-551429-C-T is described in ClinVar as [Benign]. Clinvar id is 791569.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-551429-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.989 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00221 (337/152254) while in subpopulation NFE AF= 0.00225 (153/68004). AF 95% confidence interval is 0.00196. There are 1 homozygotes in gnomad4. There are 190 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 337 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.933G>A	p.Glu311=	synonymous_variant	10/11	ENST00000537384.6	NP_001158232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.933G>A	p.Glu311=	synonymous_variant	10/11	5	NM_001164760.2	ENSP00000440449	P1

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

337

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00267

AC:

448

AN:

167896

Hom.:

AF XY:

0.00252

AC XY:

226

AN XY:

89516

show subpopulations

Gnomad AFR exome

AF:

0.000289

Gnomad AMR exome

AF:

0.000790

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000465

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.00219

GnomAD4 exome

AF:

0.00205

AC:

2888

AN:

1408272

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1466

AN XY:

695428

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.000688

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.00223

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152254

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.00225

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00303

Hom.:

Bravo

AF:

0.00144

Asia WGS

AF:

0.000577

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

5.5

DANN

Benign

0.87

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