1-204171778-G-A

Variant names:

• chr1-204171778-G-A
• rs7539596
• ENST00000638118.1:c.-17+729C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638118.1(REN):​c.-17+729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,078 control chromosomes in the GnomAD database, including 24,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24066 hom., cov: 32)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000638118.1	c.-17+729C>T		intron_variant	Intron 3 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83000 AN: 151960 Hom.: 24019 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 83101 AN: 152078 Hom.: 24066 Cov.: 32 AF XY: 0.543 AC XY: 40371 AN XY: 74316

African (AFR) AF: 0.760 AC: 31552 AN: 41516

American (AMR) AF: 0.516 AC: 7880 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1617 AN: 3466

East Asian (EAS) AF: 0.556 AC: 2873 AN: 5164

South Asian (SAS) AF: 0.425 AC: 2048 AN: 4820

European-Finnish (FIN) AF: 0.445 AC: 4695 AN: 10550

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30793 AN: 67966

Other (OTH) AF: 0.532 AC: 1121 AN: 2108

Alfa AF: 0.470 Hom.: 33062

Bravo AF: 0.562

Asia WGS AF: 0.489 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.47
PhyloP100		-1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7539596; hg19: chr1-204140906;