10-52029907-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006258.4(PRKG1):​c.763-24577A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,830 control chromosomes in the GnomAD database, including 20,375 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 0.51 ( 20375 hom., cov: 31)

Consequence

PRKG1
NM_006258.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKG1NM_006258.4 linkuse as main transcriptc.763-24577A>C intron_variant ENST00000373980.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKG1ENST00000373980.11 linkuse as main transcriptc.763-24577A>C intron_variant 1 NM_006258.4 Q13976-2
PRKG1ENST00000373976.9 linkuse as main transcriptc.763-24577A>C intron_variant 3
PRKG1ENST00000401604.8 linkuse as main transcriptc.718-24577A>C intron_variant 5 P1Q13976-1
PRKG1ENST00000645324.1 linkuse as main transcriptc.763-24577A>C intron_variant

Frequencies

GnomAD3 genomes
AF:
0.513
AC:
77831
AN:
151712
Hom.:
20338
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.612
Gnomad AMI
AF:
0.465
Gnomad AMR
AF:
0.550
Gnomad ASJ
AF:
0.449
Gnomad EAS
AF:
0.529
Gnomad SAS
AF:
0.404
Gnomad FIN
AF:
0.502
Gnomad MID
AF:
0.468
Gnomad NFE
AF:
0.457
Gnomad OTH
AF:
0.489
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.513
AC:
77928
AN:
151830
Hom.:
20375
Cov.:
31
AF XY:
0.514
AC XY:
38128
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.613
Gnomad4 AMR
AF:
0.551
Gnomad4 ASJ
AF:
0.449
Gnomad4 EAS
AF:
0.528
Gnomad4 SAS
AF:
0.405
Gnomad4 FIN
AF:
0.502
Gnomad4 NFE
AF:
0.458
Gnomad4 OTH
AF:
0.489
Alfa
AF:
0.512
Hom.:
3437
Bravo
AF:
0.527
Asia WGS
AF:
0.488
AC:
1695
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.37
DANN
Benign
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10762540; hg19: chr10-53789667; API