rs211070

Positions:

• chr10-51320512-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79

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)

ACMG classification

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
PRKG1	NM_006258.4	c.479-147211G>C		intron_variant		ENST00000373980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.479-147211G>C		intron_variant		1	NM_006258.4
RSU1P3	ENST00000412878.2	n.687G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10576 AN: 152190 Hom.: 534 Cov.: 33

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

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

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

Other links and lift over

dbSNP: rs211070; hg19: chr10-53080272;