rs11571082

chr1-204161903-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000537.4(REN):c.249+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,392,112 control chromosomes in the GnomAD database, including 12,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2312 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10448 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.326

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-204161903-C-T is Benign according to our data. Variant chr1-204161903-C-T is described in ClinVar as [Benign]. Clinvar id is 1223960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.249+110G>A		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.249+110G>A		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.135+110G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25129 AN: 151876 Hom.: 2303 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.125 AC: 154619 AN: 1240118 Hom.: 10448 AF XY: 0.125 AC XY: 76922 AN XY: 617692

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.0681

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.166 AC: 25175 AN: 151994 Hom.: 2312 Cov.: 31 AF XY: 0.164 AC XY: 12195 AN XY: 74304

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0670

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.153

Alfa AF: 0.167 Hom.: 451

Bravo AF: 0.176

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.1
Dann	Benign	0.73

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: rs11571082; hg19: chr1-204131031;