rs11000400

Variant names:

• chr10-51992715-A-C
• rs11000400
• NM_006258.4:c.763-61769A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-51992715-A-C
• chr10-51992715-A-G
• chr10-51992715-A-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.763-61769A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,062 control chromosomes in the GnomAD database, including 5,599 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 0.23 (5599 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_006258.4	c.763-61769A>C		intron_variant	Intron 5 of 17	ENST00000373980.11	NP_006249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000373980.11	c.763-61769A>C		intron_variant	Intron 5 of 17	1	NM_006258.4	ENSP00000363092.5
PRKG1	ENST00000401604.8	c.718-61769A>C		intron_variant	Intron 5 of 17	5		ENSP00000384200.4
PRKG1	ENST00000645324.1	c.763-61769A>C		intron_variant	Intron 5 of 7			ENSP00000494124.1
PRKG1	ENST00000373976.9	c.763-61769A>C		intron_variant	Intron 5 of 6	3		ENSP00000363087.4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34493 AN: 151944 Hom.: 5584 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.227 AC: 34541 AN: 152062 Hom.: 5599 Cov.: 32 AF XY: 0.229 AC XY: 17009 AN XY: 74334

African (AFR) AF: 0.443 AC: 18334 AN: 41430

American (AMR) AF: 0.177 AC: 2708 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1796 AN: 5174

South Asian (SAS) AF: 0.255 AC: 1233 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8003 AN: 67992

Other (OTH) AF: 0.214 AC: 451 AN: 2112

Alfa AF: 0.139 Hom.: 3166

Bravo AF: 0.236

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.065
DANN	Benign	0.77
PhyloP100		-0.15
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: rs11000400; hg19: chr10-53752475;