Variant chr1-204161248-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).

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/exons	MANE	UniProt
REN	NM_000537.4 linkuse as main transcript	c.373+44C>G		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9 linkuse as main transcript	c.373+44C>G		intron_variant		1	NM_000537.4	P1	P00797-1
REN	ENST00000638118.1 linkuse as main transcript	c.259+44C>G		intron_variant		5

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

GnomAD3 exomes

AF:

0.282

AC:

57836

AN:

205352

Hom.:

9106

AF XY:

0.291

AC XY:

31534

AN XY:

108432

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 SAS exome

AF:

0.272

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

Gnomad4 AFR exome

AF:

0.0531

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.257

AC:

39022

AN:

152048

Hom.:

6347

Cov.:

AF XY:

0.254

AC XY:

18878

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.262

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Familial juvenile hyperuricemic nephropathy type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Renal tubular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.74

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