Variant chr7-107159513-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002736.3(PRKAR2B):c.1188C>T(p.Ile396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,613,984 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 38 hom. )

Consequence

PRKAR2B
NM_002736.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

PRKAR2B (HGNC:9392): (protein kinase cAMP-dependent type II regulatory subunit beta) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol. [provided by RefSeq, Jul 2008]

PRKAR2B 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=-0.26).

BP6

Variant 7-107159513-C-T is Benign according to our data. Variant chr7-107159513-C-T is described in ClinVar as [Benign]. Clinvar id is 786743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.021 with no splicing effect.

BS2

High AC in GnomAd4 at 680 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAR2B	NM_002736.3 linkuse as main transcript	c.1188C>T	p.Ile396=	synonymous_variant	11/11	ENST00000265717.5	NP_002727.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAR2B	ENST00000265717.5 linkuse as main transcript	c.1188C>T	p.Ile396=	synonymous_variant	11/11	1	NM_002736.3	ENSP00000265717	P1

Frequencies

GnomAD3 genomes

AF:

0.00447

AC:

680

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00924

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00542

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00504

AC:

1267

AN:

251446

Hom.:

AF XY:

0.00595

AC XY:

808

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0151

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00506

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00507

AC:

7409

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

4009

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00723

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.00472

Gnomad4 OTH exome

AF:

0.00508

GnomAD4 genome

AF:

0.00447

AC:

680

AN:

152262

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

322

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00923

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0154

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00542

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00475

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00569

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.7

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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