rs11571084

Variant names:

• chr1-204159704-C-T
• rs11571084
• NM_000537.4:c.493-109G>A

Variant summary

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

The NM_000537.4(REN):​c.493-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 921,392 control chromosomes in the GnomAD database, including 502 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 0.025 (72 hom., cov: 32)
  • Exomes 𝑓: 0.031 (430 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3801/152268) while in subpopulation NFE AF= 0.037 (2515/68004). AF 95% confidence interval is 0.0358. There are 72 homozygotes in gnomad4. There are 1832 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3801 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.493-109G>A		intron_variant	Intron 4 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.493-109G>A		intron_variant	Intron 4 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.379-109G>A		intron_variant	Intron 6 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3804 AN: 152150 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.00652

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0401

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.0308 AC: 23727 AN: 769124 Hom.: 430 AF XY: 0.0307 AC XY: 12449 AN XY: 406090

Gnomad4 AFR exome AF: 0.00682

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0000575

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.0306

GnomAD4 genome AF: 0.0250 AC: 3801 AN: 152268 Hom.: 72 Cov.: 32 AF XY: 0.0246 AC XY: 1832 AN XY: 74452

Gnomad4 AFR AF: 0.00650

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0401

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0347 Hom.: 27

Bravo AF: 0.0231

Asia WGS AF: 0.00751 AC: 27 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	0.61
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11571084; hg19: chr1-204128832;