rs7922491

Positions:

• chr10-51733713-G-A
• chr10-51733713-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006258.4(PRKG1):​c.593-70872G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,106 control chromosomes in the GnomAD database, including 957 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 0.10 (957 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.593-70872G>A		intron_variant		ENST00000373980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.593-70872G>A		intron_variant		1	NM_006258.4

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15168 AN: 151986 Hom.: 947 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0794

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0999 AC: 15196 AN: 152106 Hom.: 957 Cov.: 32 AF XY: 0.0967 AC XY: 7189 AN XY: 74356

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0794

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0915

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.106

Alfa AF: 0.102 Hom.: 1441

Bravo AF: 0.112

Asia WGS AF: 0.122 AC: 422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs7922491; hg19: chr10-53493473;