Variant chr7-551390-G-A 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.972C>T(p.Phe324=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,556,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PRKAR1B
NM_001164760.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0001591

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.458

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=-0.59).

BP6

Variant 7-551390-G-A is Benign according to our data. Variant chr7-551390-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787312.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.458 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00184 (280/152226) while in subpopulation AFR AF= 0.00631 (262/41518). AF 95% confidence interval is 0.00568. There are 0 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR1B	NM_001164760.2 linkuse as main transcript	c.972C>T	p.Phe324=	splice_region_variant, synonymous_variant	10/11	ENST00000537384.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR1B	ENST00000537384.6 linkuse as main transcript	c.972C>T	p.Phe324=	splice_region_variant, synonymous_variant	10/11	5	NM_001164760.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000439

AC:

AN:

164108

Hom.:

AF XY:

0.000298

AC XY:

AN XY:

87238

show subpopulations

Gnomad AFR exome

AF:

0.00555

Gnomad AMR exome

AF:

0.000279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000235

Gnomad SAS exome

AF:

0.0000856

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000467

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.000197

AC:

277

AN:

1404738

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

114

AN XY:

693364

show subpopulations

Gnomad4 AFR exome

AF:

0.00625

Gnomad4 AMR exome

AF:

0.000305

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000539

Gnomad4 SAS exome

AF:

0.0000752

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.000567

GnomAD4 genome

AF:

0.00184

AC:

280

AN:

152226

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00631

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000448

Hom.:

Bravo

AF:

0.00206

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

PRKAR1B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 12, 2019

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

-0.59

CADD

Benign

0.064

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.35

SpliceAI score (max)

0.010

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