10-51467714-C-T

Variant names:

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.479-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 1,596,146 control chromosomes in the GnomAD database, including 2,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 894 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1669 hom. )

Consequence

PRKG1
NM_006258.4 intron

Scores

Splicing: ADA: 0.00001982

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.59

Publications

2 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 Gene-Disease associations (from GenCC):

aortic aneurysm, familial thoracic 8
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet

PRKG1 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=-0.85).

BP6

Variant 10-51467714-C-T is Benign according to our data. Variant chr10-51467714-C-T is described in ClinVar as Benign. ClinVar VariationId is 381780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4 link	c.479-9C>T		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.479-9C>T		intron_variant	Intron 2 of 17	1	NM_006258.4	ENSP00000363092.5		Q13976-2

Frequencies

GnomAD3 genomes

AF:

0.0799

AC:

12125

AN:

151758

Hom.:

891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0263

Gnomad EAS

AF:

0.00521

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0681

GnomAD2 exomes

AF:

0.0409

AC:

10205

AN:

249554

AF XY:

0.0371

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.00240

Gnomad FIN exome

AF:

0.0433

Gnomad NFE exome

AF:

0.0355

Gnomad OTH exome

AF:

0.0359

GnomAD4 exome

AF:

0.0394

AC:

56909

AN:

1444270

Hom.:

1669

Cov.:

AF XY:

0.0381

AC XY:

27416

AN XY:

719494

show subpopulations

African (AFR)

AF:

0.204

AC:

6735

AN:

33060

American (AMR)

AF:

0.0261

AC:

1160

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

649

AN:

25912

East Asian (EAS)

AF:

0.0111

AC:

441

AN:

39558

South Asian (SAS)

AF:

0.0233

AC:

1992

AN:

85378

European-Finnish (FIN)

AF:

0.0430

AC:

2295

AN:

53346

Middle Eastern (MID)

AF:

0.0262

AC:

150

AN:

5730

European-Non Finnish (NFE)

AF:

0.0372

AC:

40831

AN:

1097024

Other (OTH)

AF:

0.0444

AC:

2656

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2555

5109

7664

10218

12773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1648

3296

4944

6592

8240

<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:

0.0799

AC:

12137

AN:

151876

Hom.:

894

Cov.:

AF XY:

0.0781

AC XY:

5803

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.197

AC:

8153

AN:

41444

American (AMR)

AF:

0.0405

AC:

619

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

AN:

3466

East Asian (EAS)

AF:

0.00522

AC:

AN:

5174

South Asian (SAS)

AF:

0.0232

AC:

112

AN:

4826

European-Finnish (FIN)

AF:

0.0405

AC:

429

AN:

10592

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2440

AN:

67798

Other (OTH)

AF:

0.0674

AC:

142

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

530

1060

1589

2119

2649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0535

Hom.:

429

Bravo

AF:

0.0851

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 28, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 21, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aortic aneurysm, familial thoracic 8

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Jan 03, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

-0.85

CADD

Benign

0.46

(source)

DANN

Benign

0.26

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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

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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