rs2887284

Variant names:

• chr1-204155520-C-A
• rs2887284
• NM_000537.4:c.1059+300G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204155520-C-A
• chr1-204155520-C-G

Variant summary

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

The NM_000537.4(REN):​c.1059+300G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,044 control chromosomes in the GnomAD database, including 3,582 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 0.22 (3582 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.1059+300G>T		intron_variant	Intron 9 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.1059+300G>T		intron_variant	Intron 9 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.945+300G>T		intron_variant	Intron 11 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33341 AN: 151926 Hom.: 3578 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.219 AC: 33366 AN: 152044 Hom.: 3582 Cov.: 32 AF XY: 0.218 AC XY: 16226 AN XY: 74304

African (AFR) AF: 0.236 AC: 9779 AN: 41458

American (AMR) AF: 0.225 AC: 3438 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3470

East Asian (EAS) AF: 0.190 AC: 983 AN: 5164

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4816

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10568

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14217 AN: 67980

Other (OTH) AF: 0.219 AC: 462 AN: 2110

Alfa AF: 0.212 Hom.: 2536

Bravo AF: 0.222

Asia WGS AF: 0.196 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.45
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2887284; hg19: chr1-204124648;