rs5705

Positions:

chr1-204162058-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000537.4(REN):c.204A>C(p.Thr68=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,772 control chromosomes in the GnomAD database, including 16,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2924 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13126 hom. )

Consequence

REN
NM_000537.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.627

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-204162058-T-G is Benign according to our data. Variant chr1-204162058-T-G is described in ClinVar as [Benign]. Clinvar id is 256379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-204162058-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4 linkuse as main transcript	c.204A>C	p.Thr68=	synonymous_variant	2/10	ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9 linkuse as main transcript	c.204A>C	p.Thr68=	synonymous_variant	2/10	1	NM_000537.4	P1	P00797-1
REN	ENST00000638118.1 linkuse as main transcript	c.90A>C	p.Thr30=	synonymous_variant	4/12	5

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27252

AN:

151926

Hom.:

2915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.0913

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.141

AC:

35385

AN:

251010

Hom.:

2866

AF XY:

0.136

AC XY:

18519

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0882

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.128

AC:

187069

AN:

1461728

Hom.:

13126

Cov.:

AF XY:

0.128

AC XY:

92719

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.0831

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.180

AC:

27304

AN:

152044

Hom.:

2924

Cov.:

AF XY:

0.178

AC XY:

13224

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.0913

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.138

Hom.:

2601

Bravo

AF:

0.192

Asia WGS

AF:

0.134

AC:

468

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Renal tubular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial juvenile hyperuricemic nephropathy type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.2

DANN

Benign

0.23

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