rs12750834

chr1-204171656-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638118.1(REN):c.-17+851C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,032 control chromosomes in the GnomAD database, including 2,896 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 0.19 (2896 hom., cov: 32)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000638118.1	c.-17+851C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28794 AN: 151914 Hom.: 2893 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.190 AC: 28823 AN: 152032 Hom.: 2896 Cov.: 32 AF XY: 0.191 AC XY: 14224 AN XY: 74324

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.185

Alfa AF: 0.181 Hom.: 488

Bravo AF: 0.190

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.3
Dann	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12750834; hg19: chr1-204140784;