rs11571079

Positions:

• chr1-204163662-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000537.4(REN):​c.99-1499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,284 control chromosomes in the GnomAD database, including 132 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 0.036 (132 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.036 (5487/152284) while in subpopulation NFE AF= 0.0501 (3409/68032). AF 95% confidence interval is 0.0487. There are 132 homozygotes in gnomad4. There are 2607 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5487 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.99-1499G>A		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.99-1499G>A		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.-16-1499G>A		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5481 AN: 152166 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0388

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

GnomAD4 genome AF: 0.0360 AC: 5487 AN: 152284 Hom.: 132 Cov.: 32 AF XY: 0.0350 AC XY: 2607 AN XY: 74472

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0299

Gnomad4 FIN AF: 0.0413

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0436 Hom.: 26

Bravo AF: 0.0353

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11571079; hg19: chr1-204132790;