rs7897633

Variant names:

• chr10-51197961-C-A
• rs7897633
• NM_006258.4:c.478+44631C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006258.4(PRKG1):​c.478+44631C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,516 control chromosomes in the GnomAD database, including 31,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31448 hom., cov: 29)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 23 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006258.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_006258.4	MANE Select	c.478+44631C>A		intron	N/A	NP_006249.1
	PRKG1	NM_001098512.3		c.433+44631C>A		intron	N/A	NP_001091982.1
	PRKG1	NM_001374782.1		c.478+44631C>A		intron	N/A	NP_001361711.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.478+44631C>A		intron	N/A	ENSP00000363092.5
	PRKG1	ENST00000401604.8	TSL:5	c.433+44631C>A		intron	N/A	ENSP00000384200.4
	PRKG1	ENST00000645324.1		c.478+44631C>A		intron	N/A	ENSP00000494124.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95523 AN: 151396 Hom.: 31378 Cov.: 29

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 95659 AN: 151516 Hom.: 31448 Cov.: 29 AF XY: 0.626 AC XY: 46335 AN XY: 74038

African (AFR) AF: 0.836 AC: 34616 AN: 41390

American (AMR) AF: 0.580 AC: 8841 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2237 AN: 5078

South Asian (SAS) AF: 0.523 AC: 2498 AN: 4778

European-Finnish (FIN) AF: 0.578 AC: 6072 AN: 10510

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37558 AN: 67752

Other (OTH) AF: 0.620 AC: 1309 AN: 2112

Alfa AF: 0.569 Hom.: 77249

Bravo AF: 0.637

Asia WGS AF: 0.546 AC: 1901 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.38
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7897633; hg19: chr10-52957721;