10-51467269-T-C

Position:

• chr10-51467269-T-C

Variant summary

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

The ENST00000373980.11(PRKG1):​c.479-454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,748 control chromosomes in the GnomAD database, including 15,831 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 0.45 (15831 hom., cov: 32)
• Consequence: PRKG1 ENST00000373980.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.479-454T>C		intron_variant		ENST00000373980.11	NP_006249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.479-454T>C		intron_variant		1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67929 AN: 151628 Hom.: 15820 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.448 AC: 67970 AN: 151748 Hom.: 15831 Cov.: 32 AF XY: 0.442 AC XY: 32810 AN XY: 74178

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.436

Alfa AF: 0.433 Hom.: 6593

Bravo AF: 0.439

Asia WGS AF: 0.241 AC: 840 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.071
DANN	Benign	0.41

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: rs10997653; hg19: chr10-53227029;