rs11571078

chr1-204164046-G-Achr1-204164046-G-T

Variant summary

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

The NM_000537.4(REN):c.99-1883C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,106 control chromosomes in the GnomAD database, including 3,114 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 0.18 (3114 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.99-1883C>T		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.99-1883C>T		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.-16-1883C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27504 AN: 151988 Hom.: 3105 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.181 AC: 27543 AN: 152106 Hom.: 3114 Cov.: 32 AF XY: 0.177 AC XY: 13189 AN XY: 74360

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.186

Alfa AF: 0.158 Hom.: 367

Bravo AF: 0.187

Asia WGS AF: 0.141 AC: 490 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	4.6
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11571078; hg19: chr1-204133174;