rs5707

Positions:

• chr1-204160543-A-C
• chr1-204160543-A-G
• chr1-204160543-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000272190.9(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 ENST00000272190.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0520

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 256380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-204160543-A-C is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.492+17T>G		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.492+17T>G		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.378+17T>G		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38059 AN: 152066 Hom.: 4943 Cov.: 32

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

GnomAD3 exomes AF: 0.253 AC: 63441 AN: 251134 Hom.: 8384 AF XY: 0.249 AC XY: 33767 AN XY: 135756

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 SAS exome AF: 0.222

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.: 26 AF XY: 0.237 AC XY: 167001 AN XY: 705858

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.250 AC: 38086 AN: 152186 Hom.: 4947 Cov.: 32 AF XY: 0.250 AC XY: 18584 AN XY: 74422

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.250

Alfa AF: 0.224 Hom.: 4011

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

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 18192836) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Kidney disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Renal tubular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Familial juvenile hyperuricemic nephropathy type 2 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	-0.87
CADD	Benign	6.8
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs5707; hg19: chr1-204129671;