Variant chr1-204155078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PVS1_ModeratePM2PP5BS2

The NM_000537.4(REN):c.1159C>T(p.Arg387Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000342 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

REN
NM_000537.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

REN (HGNC:9958): (renin) This gene encodes renin, an aspartic protease that is secreted by the kidneys. Renin is a part of the renin-angiotensin-aldosterone system involved in regulation of blood pressure, and electrolyte balance. This enzyme catalyzes the first step in the activation pathway of angiotensinogen by cleaving angiotensinogen to form angiotensin I, which is then converted to angiotensin II by angiotensin I converting enzyme. This cascade can result in aldosterone release, narrowing of blood vessels, and increase in blood pressure as angiotension II is a vasoconstrictive peptide. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause hyperuricemic nephropathy familial juvenile 2, familial hyperproreninemia, and renal tubular dysgenesis. [provided by RefSeq, May 2020]

REN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0508 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-204155078-G-A is Pathogenic according to our data. Variant chr1-204155078-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 13122.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4 linkuse as main transcript	c.1159C>T	p.Arg387Ter	stop_gained	10/10	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9 linkuse as main transcript	c.1159C>T	p.Arg387Ter	stop_gained	10/10	1	NM_000537.4	ENSP00000272190	P1	P00797-1
REN	ENST00000638118.1 linkuse as main transcript	c.1045C>T	p.Arg349Ter	stop_gained	12/12	5		ENSP00000490307

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hyperproreninemia, familial

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 02, 1994

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.60

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.91

MutationTaster

Benign

1.0

A;A

Vest4

0.60

GERP RS

4.1

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