rs3730103

chr1-204156859-T-C

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.699-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 1,603,728 control chromosomes in the GnomAD database, including 6,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1974 hom., cov: 32)
  • Exomes 𝑓: 0.064 (4085 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337

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=-0.89).
• BP6: Variant 1-204156859-T-C is Benign according to our data. Variant chr1-204156859-T-C is described in ClinVar as [Benign]. Clinvar id is 1247423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.699-63A>G		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.699-63A>G		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.585-63A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17994 AN: 151954 Hom.: 1971 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0635 AC: 92187 AN: 1451656 Hom.: 4085 AF XY: 0.0624 AC XY: 45081 AN XY: 722704

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.0504

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0448

Gnomad4 FIN exome AF: 0.0540

Gnomad4 NFE exome AF: 0.0615

Gnomad4 OTH exome AF: 0.0679

GnomAD4 genome AF: 0.119 AC: 18026 AN: 152072 Hom.: 1974 Cov.: 32 AF XY: 0.115 AC XY: 8540 AN XY: 74370

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0729 Hom.: 216

Bravo AF: 0.128

Asia WGS AF: 0.0290 AC: 103 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.2
Dann	Benign	0.44

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: rs3730103; hg19: chr1-204125987;