rs5707

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000537.4(REN):c.492+17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,564,664 control chromosomes in the GnomAD database, including 46,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4947 hom., cov: 32)

Exomes 𝑓: 0.24 ( 41226 hom. )

Consequence

REN
NM_000537.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0520

Publications

30 publications found

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 Gene-Disease associations (from GenCC):

familial juvenile hyperuricemic nephropathy type 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics

REN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-204160543-A-C is Benign according to our data. Variant chr1-204160543-A-C is described in ClinVar as Benign. ClinVar VariationId is 256380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4 link	c.492+17T>G		intron_variant	Intron 4 of 9	ENST00000272190.9	NP_000528.1	P00797-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9 link	c.492+17T>G		intron_variant	Intron 4 of 9	1	NM_000537.4	ENSP00000272190.8		P00797-1
REN	ENST00000638118.1 link	c.378+17T>G		intron_variant	Intron 6 of 11	5		ENSP00000490307.1		A0A1B0GUZ2

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38059

AN:

152066

Hom.:

4943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.251

GnomAD2 exomes

AF:

0.253

AC:

63441

AN:

251134

AF XY:

0.249

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.423

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.238

AC:

336155

AN:

1412478

Hom.:

41226

Cov.:

AF XY:

0.237

AC XY:

167001

AN XY:

705858

show subpopulations

African (AFR)

AF:

0.271

AC:

8818

AN:

32516

American (AMR)

AF:

0.263

AC:

11742

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5911

AN:

25820

East Asian (EAS)

AF:

0.417

AC:

16466

AN:

39452

South Asian (SAS)

AF:

0.220

AC:

18774

AN:

85252

European-Finnish (FIN)

AF:

0.238

AC:

12691

AN:

53378

Middle Eastern (MID)

AF:

0.254

AC:

1442

AN:

5684

European-Non Finnish (NFE)

AF:

0.230

AC:

245838

AN:

1066942

Other (OTH)

AF:

0.246

AC:

14473

AN:

58788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12948

25895

38843

51790

64738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8478

16956

25434

33912

42390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.250

AC:

38086

AN:

152186

Hom.:

4947

Cov.:

AF XY:

0.250

AC XY:

18584

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.272

AC:

11297

AN:

41516

American (AMR)

AF:

0.249

AC:

3809

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3468

East Asian (EAS)

AF:

0.415

AC:

2147

AN:

5178

South Asian (SAS)

AF:

0.217

AC:

1046

AN:

4828

European-Finnish (FIN)

AF:

0.232

AC:

2460

AN:

10606

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.231

AC:

15693

AN:

67982

Other (OTH)

AF:

0.250

AC:

529

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1468

2936

4405

5873

7341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.225

Hom.:

5156

Bravo

AF:

0.253

Asia WGS

AF:

0.292

AC:

1013

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18192836) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kidney disorder

Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial juvenile hyperuricemic nephropathy type 2

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal tubular dysgenesis

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

(source)

DANN

Benign

0.38

PhyloP100

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over