Variant 10-50991227-A-G 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.-152A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,162,506 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 49 hom., cov: 29)

Exomes 𝑓: 0.012 ( 190 hom. )

Consequence

PRKG1
NM_001098512.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0580

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=-0.81).

BP6

Variant 10-50991227-A-G is Benign according to our data. Variant chr10-50991227-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 676360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2943/152070) while in subpopulation AFR AF= 0.0421 (1748/41492). AF 95% confidence interval is 0.0405. There are 49 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG1	NM_001098512.3 link	c.-152A>G		5_prime_UTR_variant	Exon 1 of 18		NP_001091982.1	Q13976-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG1	ENST00000401604 link	c.-152A>G		5_prime_UTR_variant	Exon 1 of 18	5		ENSP00000384200.4		Q13976-1

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2932

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0221

GnomAD4 exome

AF:

0.0121

AC:

12269

AN:

1010436

Hom.:

190

Cov.:

AF XY:

0.0122

AC XY:

6160

AN XY:

502864

show subpopulations

Gnomad4 AFR exome

AF:

0.0405

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.00497

Gnomad4 EAS exome

AF:

0.0000361

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0135

GnomAD4 genome

AF:

0.0194

AC:

2943

AN:

152070

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1432

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0421

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.00895

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

Jun 14, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.50

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