Variant rs2043556 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006258.4(PRKG1):c.478+146316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 461,234 control chromosomes in the GnomAD database, including 14,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4677 hom., cov: 32)

Exomes 𝑓: 0.24 ( 10002 hom. )

Consequence

PRKG1
NM_006258.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.634

Variant links:

Genes affected

PRKG1 (HGNC:9414): (protein kinase cGMP-dependent 1) Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]

PRKG1 links:

MIR605 (HGNC:):

MIR605 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 10-51299646-T-C is Benign according to our data. Variant chr10-51299646-T-C is described in ClinVar as [Benign]. Clinvar id is 1232610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG1	NM_006258.4 linkuse as main transcript	c.478+146316T>C		intron_variant		ENST00000373980.11	NP_006249.1	Q13976-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11 linkuse as main transcript	c.478+146316T>C		intron_variant		1	NM_006258.4	ENSP00000363092.5		Q13976-2

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37279

AN:

151836

Hom.:

4669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.254

AC:

37396

AN:

147162

Hom.:

5283

AF XY:

0.250

AC XY:

19687

AN XY:

78674

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.246

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.243

AC:

75193

AN:

309280

Hom.:

10002

Cov.:

AF XY:

0.243

AC XY:

42832

AN XY:

175926

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.432

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.246

AC:

37323

AN:

151954

Hom.:

4677

Cov.:

AF XY:

0.249

AC XY:

18465

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.223

Hom.:

5750

Bravo

AF:

0.256

Asia WGS

AF:

0.253

AC:

880

AN:

3478

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	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 25683625) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.4

DANN

Benign

0.64

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