chr10-52283811-G-T

Variant names:

• chr10-52283811-G-T
• rs11001447
• NM_006258.4:c.1709+1495G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006258.4(PRKG1):​c.1709+1495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,690 control chromosomes in the GnomAD database, including 19,015 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 0.47 (19015 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.1709+1495G>T		intron_variant	Intron 14 of 17	ENST00000373980.11	NP_006249.1
PRKG1	NM_001098512.3	c.1664+1495G>T		intron_variant	Intron 14 of 17		NP_001091982.1
PRKG1	NM_001374781.1	c.500+1495G>T		intron_variant	Intron 10 of 13		NP_001361710.1
PRKG1	XM_017016413.2	c.1406+1495G>T		intron_variant	Intron 14 of 17		XP_016871902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.1709+1495G>T		intron_variant	Intron 14 of 17	1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72005 AN: 151572 Hom.: 19018 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.539

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.475 AC: 72006 AN: 151690 Hom.: 19015 Cov.: 32 AF XY: 0.473 AC XY: 35069 AN XY: 74112

African (AFR) AF: 0.239 AC: 9890 AN: 41394

American (AMR) AF: 0.434 AC: 6598 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2634 AN: 5144

South Asian (SAS) AF: 0.454 AC: 2180 AN: 4798

European-Finnish (FIN) AF: 0.580 AC: 6114 AN: 10536

Middle Eastern (MID) AF: 0.528 AC: 152 AN: 288

European-Non Finnish (NFE) AF: 0.605 AC: 41058 AN: 67854

Other (OTH) AF: 0.499 AC: 1048 AN: 2100

Alfa AF: 0.543 Hom.: 10215

Bravo AF: 0.452

Asia WGS AF: 0.471 AC: 1621 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.29
PhyloP100		-1.1
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: rs11001447; hg19: chr10-54043571;