Variant 10-50991778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001098512.3(PRKG1):c.266+134C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 582,828 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

PRKG1
NM_001098512.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.630

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 10-50991778-C-A is Benign according to our data. Variant chr10-50991778-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1218770.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00462 (699/151252) while in subpopulation AFR AF= 0.0161 (667/41390). AF 95% confidence interval is 0.0151. There are 3 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 699 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3 linkuse as main transcript	c.266+134C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8 linkuse as main transcript	c.266+134C>A		intron_variant		5		P1	Q13976-1

Frequencies

GnomAD3 genomes

AF:

0.00462

AC:

699

AN:

151142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000886

Gnomad OTH

AF:

0.00384

GnomAD4 exome

AF:

0.000412

AC:

178

AN:

431576

Hom.:

AF XY:

0.000396

AC XY:

AN XY:

204696

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.000924

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000835

GnomAD4 genome

AF:

0.00462

AC:

699

AN:

151252

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

314

AN XY:

73900

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000886

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00547

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

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

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