rs10823978

Variant names:

• chr10-52028197-G-A
• rs10823978
• NM_006258.4:c.763-26287G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-52028197-G-A
• chr10-52028197-G-C
• chr10-52028197-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.763-26287G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,916 control chromosomes in the GnomAD database, including 4,315 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 0.22 (4315 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• 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

ENSG00000289527 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.763-26287G>A		intron_variant	Intron 5 of 17	ENST00000373980.11	NP_006249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.763-26287G>A		intron_variant	Intron 5 of 17	1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34107 AN: 151796 Hom.: 4314 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.225 AC: 34132 AN: 151916 Hom.: 4315 Cov.: 32 AF XY: 0.230 AC XY: 17058 AN XY: 74214

African (AFR) AF: 0.120 AC: 4965 AN: 41440

American (AMR) AF: 0.306 AC: 4677 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1196 AN: 5166

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3444 AN: 10502

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.248 AC: 16884 AN: 67950

Other (OTH) AF: 0.214 AC: 452 AN: 2108

Alfa AF: 0.228 Hom.: 2626

Bravo AF: 0.222

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.56
PhyloP100		1.2
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: rs10823978; hg19: chr10-53787957;