rs211070

Variant summary

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

The NM_006258.4(PRKG1):​c.479-147211G>C variant causes a intron change. The variant allele was found at a frequency of 0.0694 in 153,298 control chromosomes in the GnomAD database, including 540 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 0.070 ( 538 hom., cov: 33)
Exomes 𝑓: 0.026 ( 2 hom. )

Consequence

PRKG1
NM_006258.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.79
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]
RSU1P3 (HGNC:44392): (Ras suppressor protein 1 pseudogene 3)

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=-0.63).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKG1NM_006258.4 linkuse as main transcriptc.479-147211G>C intron_variant ENST00000373980.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKG1ENST00000373980.11 linkuse as main transcriptc.479-147211G>C intron_variant 1 NM_006258.4 Q13976-2
RSU1P3ENST00000412878.2 linkuse as main transcriptn.687G>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0695
AC:
10576
AN:
152190
Hom.:
534
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.141
Gnomad AMI
AF:
0.147
Gnomad AMR
AF:
0.0419
Gnomad ASJ
AF:
0.0556
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.0755
Gnomad FIN
AF:
0.0232
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0446
Gnomad OTH
AF:
0.0521
GnomAD4 exome
AF:
0.0263
AC:
26
AN:
990
Hom.:
2
Cov.:
0
AF XY:
0.0287
AC XY:
19
AN XY:
662
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0238
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0271
Gnomad4 OTH exome
AF:
0.0185
GnomAD4 genome
AF:
0.0697
AC:
10610
AN:
152308
Hom.:
538
Cov.:
33
AF XY:
0.0678
AC XY:
5050
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.141
Gnomad4 AMR
AF:
0.0418
Gnomad4 ASJ
AF:
0.0556
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.0758
Gnomad4 FIN
AF:
0.0232
Gnomad4 NFE
AF:
0.0446
Gnomad4 OTH
AF:
0.0515
Alfa
AF:
0.0539
Hom.:
30
Bravo
AF:
0.0743
Asia WGS
AF:
0.0490
AC:
170
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
13
DANN
Benign
0.54

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: rs211070; hg19: chr10-53080272; API