rs2043556

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

83 publications found

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:32861): (microRNA 605) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR605 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PRKG1	NM_006258.4 link	c.478+146316T>C		intron_variant	Intron 2 of 17	ENST00000373980.11	NP_006249.1	Q13976-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11 link	c.478+146316T>C		intron_variant	Intron 2 of 17	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

GnomAD2 exomes

AF:

0.254

AC:

37396

AN:

147162

AF XY:

0.250

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 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

African (AFR)

AF:

0.233

AC:

1854

AN:

7968

American (AMR)

AF:

0.432

AC:

10928

AN:

25282

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

2602

AN:

10876

East Asian (EAS)

AF:

0.258

AC:

2230

AN:

8652

South Asian (SAS)

AF:

0.249

AC:

14774

AN:

59260

European-Finnish (FIN)

AF:

0.238

AC:

5466

AN:

22988

Middle Eastern (MID)

AF:

0.251

AC:

687

AN:

2738

European-Non Finnish (NFE)

AF:

0.212

AC:

33407

AN:

157426

Other (OTH)

AF:

0.230

AC:

3245

AN:

14090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

2705

5409

8114

10818

13523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.246

AC:

37323

AN:

151954

Hom.:

4677

Cov.:

AF XY:

0.249

AC XY:

18465

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.244

AC:

10107

AN:

41476

American (AMR)

AF:

0.371

AC:

5671

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

879

AN:

3462

East Asian (EAS)

AF:

0.271

AC:

1394

AN:

5140

South Asian (SAS)

AF:

0.242

AC:

1168

AN:

4826

European-Finnish (FIN)

AF:

0.246

AC:

2593

AN:

10562

Middle Eastern (MID)

AF:

0.210

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.217

AC:

14704

AN:

67914

Other (OTH)

AF:

0.265

AC:

558

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1314

2628

3941

5255

6569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.226

Hom.:

7383

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

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25683625) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.4

(source)

DANN

Benign

0.64

PhyloP100

-0.63

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over