rs115808289

Variant names:

• chr10-52251362-G-A
• rs115808289
• NM_006258.4:c.1077-208G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006258.4(PRKG1):​c.1077-208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 152,146 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0071 (12 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510
• Publications: 0 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-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

LOC124902425 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-52251362-G-A is Benign according to our data. Variant chr10-52251362-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1196404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00707 (1075/152146) while in subpopulation AFR AF = 0.0245 (1016/41524). AF 95% confidence interval is 0.0232. There are 12 homozygotes in GnomAd4. There are 493 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1075 AD,Unknown gene.

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.1077-208G>A		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.1032-208G>A		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374781.1		c.-133-208G>A		intron	N/A	NP_001361710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.1077-208G>A		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1	ENST00000401604.8	TSL:5	c.1032-208G>A		intron	N/A	ENSP00000384200.4	Q13976-1
	PRKG1	ENST00000672084.1		c.228-208G>A		intron	N/A	ENSP00000499822.1	A0A5F9ZGW0

Frequencies

GnomAD3 genomes AF: 0.00704 AC: 1070 AN: 152026 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00718

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

GnomAD4 genome AF: 0.00707 AC: 1075 AN: 152146 Hom.: 12 Cov.: 32 AF XY: 0.00663 AC XY: 493 AN XY: 74370

African (AFR) AF: 0.0245 AC: 1016 AN: 41524

American (AMR) AF: 0.00223 AC: 34 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68000

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00520 Hom.: 0

Bravo AF: 0.00767

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.46
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism

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: rs115808289; hg19: chr10-54011122; COSMIC: COSV64766673; COSMIC: COSV64766673;