rs7097311

Variant names:

• chr10-51081612-A-G
• rs7097311
• NM_006258.4:c.311+6711A>G

Variant summary

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

The ENST00000373980.11(PRKG1):​c.311+6711A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,130 control chromosomes in the GnomAD database, including 5,036 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 0.25 (5036 hom., cov: 32)
• Consequence: PRKG1 ENST00000373980.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373980.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_006258.4	MANE Select	c.311+6711A>G		intron	N/A	NP_006249.1
	PRKG1	NM_001098512.3		c.267-71552A>G		intron	N/A	NP_001091982.1
	PRKG1	NM_001374782.1		c.311+6711A>G		intron	N/A	NP_001361711.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.311+6711A>G		intron	N/A	ENSP00000363092.5
	PRKG1	ENST00000401604.8	TSL:5	c.267-71552A>G		intron	N/A	ENSP00000384200.4
	PRKG1	ENST00000645324.1		c.311+6711A>G		intron	N/A	ENSP00000494124.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38306 AN: 152012 Hom.: 5033 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.252 AC: 38331 AN: 152130 Hom.: 5036 Cov.: 32 AF XY: 0.245 AC XY: 18254 AN XY: 74362

African (AFR) AF: 0.303 AC: 12587 AN: 41500

American (AMR) AF: 0.275 AC: 4197 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3464

East Asian (EAS) AF: 0.0634 AC: 328 AN: 5172

South Asian (SAS) AF: 0.128 AC: 615 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2365 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16597 AN: 67978

Other (OTH) AF: 0.266 AC: 562 AN: 2114

Alfa AF: 0.246 Hom.: 19325

Bravo AF: 0.261

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.69
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7097311; hg19: chr10-52841372;