Variant chr10-50991235-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001098512.3(PRKG1):c.-144C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,222,170 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 61 hom., cov: 29)

Exomes 𝑓: 0.020 ( 401 hom. )

Consequence

PRKG1
NM_001098512.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-50991235-C-A is Benign according to our data. Variant chr10-50991235-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 674736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0253 (3847/152148) while in subpopulation EAS AF= 0.0401 (206/5140). AF 95% confidence interval is 0.0356. There are 61 homozygotes in gnomad4. There are 1923 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3847 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3 linkuse as main transcript	c.-144C>A		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8 linkuse as main transcript	c.-144C>A		5_prime_UTR_variant	1/18	5		P1	Q13976-1

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3843

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0327

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0398

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.0329

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.0198

AC:

21206

AN:

1070022

Hom.:

401

Cov.:

AF XY:

0.0198

AC XY:

10501

AN XY:

530074

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.0483

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0333

Gnomad4 NFE exome

AF:

0.0184

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0253

AC:

3847

AN:

152148

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1923

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.0401

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.0329

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0287

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over