chr10-51197961-C-A

Position:

• chr10-51197961-C-A

Variant summary

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

The NM_006258.4(PRKG1):​c.478+44631C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,516 control chromosomes in the GnomAD database, including 31,448 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 0.63 (31448 hom., cov: 29)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.478+44631C>A		intron_variant		ENST00000373980.11	NP_006249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.478+44631C>A		intron_variant		1	NM_006258.4	ENSP00000363092

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95523 AN: 151396 Hom.: 31378 Cov.: 29

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.631 AC: 95659 AN: 151516 Hom.: 31448 Cov.: 29 AF XY: 0.626 AC XY: 46335 AN XY: 74038

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.620

Alfa AF: 0.560 Hom.: 31820

Bravo AF: 0.637

Asia WGS AF: 0.546 AC: 1901 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7897633; hg19: chr10-52957721;