Variant chr7-550610-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001164760.2(PRKAR1B):c.974-8A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,548,320 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 121 hom., cov: 32)

Exomes 𝑓: 0.010 ( 749 hom. )

Consequence

PRKAR1B
NM_001164760.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001114

Clinical Significance

Benign no assertion criteria provided B:3

Conservation

PhyloP100: 0.532

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=-0.91).

BP6

Variant 7-550610-T-G is Benign according to our data. Variant chr7-550610-T-G is described in ClinVar as [Benign]. Clinvar id is 1209930.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-550610-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.974-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000537384.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.974-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001164760.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3323

AN:

151396

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00755

Gnomad ASJ

AF:

0.00664

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.00124

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.0207

GnomAD3 exomes

AF:

0.0220

AC:

4008

AN:

182266

Hom.:

227

AF XY:

0.0206

AC XY:

2042

AN XY:

99192

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00376

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0100

AC:

14005

AN:

1396804

Hom.:

749

Cov.:

AF XY:

0.0101

AC XY:

6972

AN XY:

689328

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.00393

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0220

AC:

3330

AN:

151516

Hom.:

121

Cov.:

AF XY:

0.0229

AC XY:

1692

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.0479

Gnomad4 AMR

AF:

0.00748

Gnomad4 ASJ

AF:

0.00664

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.0169

Gnomad4 FIN

AF:

0.00124

Gnomad4 NFE

AF:

0.00425

Gnomad4 OTH

AF:

0.0200

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.0750

AC:

263

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

PRKAR1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

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

-0.91

CADD

Benign

3.5

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0040

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