10-52286657-A-T

Position:

• chr10-52286657-A-T

Variant summary

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

The NM_006258.4(PRKG1):​c.1710-2069A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,712 control chromosomes in the GnomAD database, including 19,499 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 0.49 (19499 hom., cov: 31)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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)

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 (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.1710-2069A>T		intron_variant		ENST00000373980.11
PRKG1	NM_001098512.3	c.1665-2069A>T		intron_variant
PRKG1	NM_001374781.1	c.501-2069A>T		intron_variant
PRKG1	XM_017016413.2	c.1407-2069A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.1710-2069A>T		intron_variant		1	NM_006258.4
PRKG1-AS1	ENST00000452247.7	n.461+7258T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73907 AN: 151594 Hom.: 19500 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.487 AC: 73919 AN: 151712 Hom.: 19499 Cov.: 31 AF XY: 0.485 AC XY: 35984 AN XY: 74140

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.503

Alfa AF: 0.548 Hom.: 2957

Bravo AF: 0.467

Asia WGS AF: 0.467 AC: 1598 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.68

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: rs11001456; hg19: chr10-54046417;