rs1937652

Variant names:

• chr10-51805558-G-A
• rs1937652
• NM_006258.4:c.698+868G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-51805558-G-A
• chr10-51805558-G-C
• chr10-51805558-G-T

Variant summary

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

The NM_006258.4(PRKG1):​c.698+868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,748 control chromosomes in the GnomAD database, including 32,980 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 0.66 (32980 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• 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, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 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.698+868G>A		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.653+868G>A		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374782.1		c.698+868G>A		intron	N/A	NP_001361711.1	B1ALS0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.698+868G>A		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1	ENST00000401604.8	TSL:5	c.653+868G>A		intron	N/A	ENSP00000384200.4	Q13976-1
	PRKG1	ENST00000645324.1		c.698+868G>A		intron	N/A	ENSP00000494124.1	A0A2R8Y507

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99633 AN: 151632 Hom.: 32964 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.657 AC: 99692 AN: 151748 Hom.: 32980 Cov.: 32 AF XY: 0.654 AC XY: 48486 AN XY: 74162

African (AFR) AF: 0.669 AC: 27743 AN: 41466

American (AMR) AF: 0.544 AC: 8284 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2486 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2848 AN: 5142

South Asian (SAS) AF: 0.578 AC: 2783 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 6970 AN: 10516

Middle Eastern (MID) AF: 0.737 AC: 196 AN: 266

European-Non Finnish (NFE) AF: 0.683 AC: 46352 AN: 67844

Other (OTH) AF: 0.656 AC: 1378 AN: 2100

Alfa AF: 0.658 Hom.: 12333

Bravo AF: 0.653

Asia WGS AF: 0.543 AC: 1859 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		0.092
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: rs1937652; hg19: chr10-53565318;