rs211070

Variant names:

• chr10-51320512-G-C
• rs211070
• NM_006258.4:c.479-147211G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006258.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_006258.4	MANE Select	c.479-147211G>C		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.434-147211G>C		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374782.1		c.479-147211G>C		intron	N/A	NP_001361711.1	B1ALS0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.479-147211G>C		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1	ENST00000401604.8	TSL:5	c.434-147211G>C		intron	N/A	ENSP00000384200.4	Q13976-1
	PRKG1	ENST00000645324.1		c.479-147211G>C		intron	N/A	ENSP00000494124.1	A0A2R8Y507

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

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0238 AC: 1 AN: 42

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36

Middle Eastern (MID) AF: 0.0329 AC: 10 AN: 304

European-Non Finnish (NFE) AF: 0.0271 AC: 14 AN: 516

Other (OTH) AF: 0.0185 AC: 1 AN: 54

GnomAD4 genome AF: 0.0697 AC: 10610 AN: 152308 Hom.: 538 Cov.: 33 AF XY: 0.0678 AC XY: 5050 AN XY: 74478

African (AFR) AF: 0.141 AC: 5864 AN: 41556

American (AMR) AF: 0.0418 AC: 639 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0758 AC: 366 AN: 4828

European-Finnish (FIN) AF: 0.0232 AC: 246 AN: 10622

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3036 AN: 68024

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.54
PhyloP100		4.8
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: rs211070; hg19: chr10-53080272;