rs11001210

chr10-52214034-C-T

Variant summary

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

The NM_006258.4(PRKG1):c.1077-37536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,156 control chromosomes in the GnomAD database, including 210 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 0.045 (210 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

LOC124902425 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_006258.4	c.1077-37536C>T		intron_variant		ENST00000373980.11
LOC124902425	XR_007062145.1	n.148-16315G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000373980.11	c.1077-37536C>T		intron_variant		1	NM_006258.4
PRKG1	ENST00000401604.8	c.1032-37536C>T		intron_variant		5		P1
PRKG1	ENST00000672084.1	c.228-37536C>T		intron_variant
PRKG1	ENST00000373975.3	n.436-37536C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6882 AN: 152038 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0452 AC: 6879 AN: 152156 Hom.: 210 Cov.: 32 AF XY: 0.0444 AC XY: 3302 AN XY: 74388

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0612 Hom.: 164

Bravo AF: 0.0436

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.35
Dann	Benign	0.66

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: rs11001210; hg19: chr10-53973794;