chr1-204155242-AC-A

Position:

• chr1-204155242-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000537.4(REN):​c.1060-66del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,568,114 control chromosomes in the GnomAD database, including 34,508 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3576 hom., cov: 27)
  • Exomes 𝑓: 0.21 (30932 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.514

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 -10 ACMG points.

• BP6: Variant 1-204155242-AC-A is Benign according to our data. Variant chr1-204155242-AC-A is described in ClinVar as [Benign]. Clinvar id is 1177782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.1060-66del		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.1060-66del		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.946-66del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33270 AN: 151228 Hom.: 3573 Cov.: 27

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.207 AC: 292602 AN: 1416768 Hom.: 30932 AF XY: 0.208 AC XY: 147055 AN XY: 707546

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.220 AC: 33293 AN: 151346 Hom.: 3576 Cov.: 27 AF XY: 0.219 AC XY: 16171 AN XY: 73910

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.219

Alfa AF: 0.216 Hom.: 359

Bravo AF: 0.222

Asia WGS AF: 0.196 AC: 683 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

- -

Computational scores

Source: dbNSFP v4.3

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: rs3215332; hg19: chr1-204124370;