Variant chr1-204155737-C-T 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.1059+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,044,162 control chromosomes in the GnomAD database, including 49,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13063 hom., cov: 32)

Exomes 𝑓: 0.28 ( 36744 hom. )

Consequence

REN
NM_000537.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.36

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=-0.97).

BP6

Variant 1-204155737-C-T is Benign according to our data. Variant chr1-204155737-C-T is described in ClinVar as [Benign]. Clinvar id is 1239591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 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.1059+83G>A		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9 linkuse as main transcript	c.1059+83G>A		intron_variant		1	NM_000537.4	P1	P00797-1
REN	ENST00000638118.1 linkuse as main transcript	c.945+83G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57088

AN:

151912

Hom.:

13021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.275

AC:

245489

AN:

892132

Hom.:

36744

AF XY:

0.275

AC XY:

126577

AN XY:

461042

show subpopulations

Gnomad4 AFR exome

AF:

0.678

Gnomad4 AMR exome

AF:

0.296

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.262

Gnomad4 OTH exome

AF:

0.297

GnomAD4 genome

AF:

0.376

AC:

57174

AN:

152030

Hom.:

13063

Cov.:

AF XY:

0.371

AC XY:

27554

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.659

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.278

Hom.:

2952

Bravo

AF:

0.395

Asia WGS

AF:

0.241

AC:

843

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.61

DANN

Benign

0.79

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