rs7910428

Variant names:

• chr10-52144406-G-A
• rs7910428
• NM_006258.4:c.1001+10501G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-52144406-G-A
• chr10-52144406-G-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.1001+10501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,120 control chromosomes in the GnomAD database, including 4,473 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 0.24 (4473 hom., cov: 33)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 4 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 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 8

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006258.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	NM_006258.4	MANE Select	c.1001+10501G>A		intron	N/A	NP_006249.1
	PRKG1	NM_001098512.3		c.956+10501G>A		intron	N/A	NP_001091982.1
	PRKG1	NM_001374781.1		c.-209+10501G>A		intron	N/A	NP_001361710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.1001+10501G>A		intron	N/A	ENSP00000363092.5
	PRKG1	ENST00000401604.8	TSL:5	c.956+10501G>A		intron	N/A	ENSP00000384200.4
	PRKG1	ENST00000672084.1		c.152+10501G>A		intron	N/A	ENSP00000499822.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35809 AN: 152002 Hom.: 4474 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.235 AC: 35817 AN: 152120 Hom.: 4473 Cov.: 33 AF XY: 0.232 AC XY: 17272 AN XY: 74366

African (AFR) AF: 0.318 AC: 13204 AN: 41458

American (AMR) AF: 0.234 AC: 3578 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1181 AN: 5178

South Asian (SAS) AF: 0.143 AC: 690 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1781 AN: 10590

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13695 AN: 67998

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.219 Hom.: 10662

Bravo AF: 0.247

Asia WGS AF: 0.179 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		-0.76
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: rs7910428; hg19: chr10-53904166;