1-204161248-G-C

Variant names:

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.373+44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,551,708 control chromosomes in the GnomAD database, including 94,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6347 hom., cov: 31)

Exomes 𝑓: 0.35 ( 88360 hom. )

Consequence

REN
NM_000537.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0330

Publications

8 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=-0.83).

BP6

Variant 1-204161248-G-C is Benign according to our data. Variant chr1-204161248-G-C is described in ClinVar as [Benign]. Clinvar id is 1268413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4 link	c.373+44C>G		intron_variant	Intron 3 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.373+44C>G		intron_variant	Intron 3 of 9	1	NM_000537.4	ENSP00000272190.8		P00797-1
REN	ENST00000638118.1 link	c.259+44C>G		intron_variant	Intron 5 of 11	5		ENSP00000490307.1		A0A1B0GUZ2

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39021

AN:

151930

Hom.:

6345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.264

GnomAD2 exomes

AF:

0.282

AC:

57836

AN:

205352

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.347

AC:

486119

AN:

1399660

Hom.:

88360

Cov.:

AF XY:

0.347

AC XY:

238830

AN XY:

688582

show subpopulations

African (AFR)

AF:

0.0531

AC:

1706

AN:

32144

American (AMR)

AF:

0.171

AC:

6724

AN:

39260

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

7251

AN:

22652

East Asian (EAS)

AF:

0.181

AC:

6904

AN:

38246

South Asian (SAS)

AF:

0.282

AC:

20886

AN:

74102

European-Finnish (FIN)

AF:

0.330

AC:

16932

AN:

51284

Middle Eastern (MID)

AF:

0.267

AC:

1469

AN:

5502

European-Non Finnish (NFE)

AF:

0.376

AC:

405656

AN:

1078670

Other (OTH)

AF:

0.322

AC:

18591

AN:

57800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13886

27771

41657

55542

69428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12834

25668

38502

51336

64170

<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:

0.257

AC:

39022

AN:

152048

Hom.:

6347

Cov.:

AF XY:

0.254

AC XY:

18878

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0636

AC:

2642

AN:

41510

American (AMR)

AF:

0.215

AC:

3290

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1090

AN:

3468

East Asian (EAS)

AF:

0.165

AC:

848

AN:

5152

South Asian (SAS)

AF:

0.289

AC:

1394

AN:

4816

European-Finnish (FIN)

AF:

0.329

AC:

3478

AN:

10564

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25203

AN:

67954

Other (OTH)

AF:

0.262

AC:

551

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1333

2666

3998

5331

6664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.304

Hom.:

1437

Bravo

AF:

0.240

Asia WGS

AF:

0.201

AC:

700

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.83

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.033

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