rs3730102

Positions:

• chr1-204157250-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000272190.9(REN):​c.698+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,407,184 control chromosomes in the GnomAD database, including 13,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1552 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11451 hom.)
• Consequence: REN ENST00000272190.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.529

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-204157250-G-A is Benign according to our data. Variant chr1-204157250-G-A is described in ClinVar as [Benign]. Clinvar id is 1281962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.698+111C>T		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.698+111C>T		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.584+111C>T		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21692 AN: 152100 Hom.: 1549 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.132 AC: 165032 AN: 1254966 Hom.: 11451 AF XY: 0.131 AC XY: 83045 AN XY: 634980

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.0863

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.143 AC: 21704 AN: 152218 Hom.: 1552 Cov.: 32 AF XY: 0.142 AC XY: 10582 AN XY: 74438

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.135

Alfa AF: 0.138 Hom.: 323

Bravo AF: 0.148

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.016
DANN	Benign	0.82

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: rs3730102; hg19: chr1-204126378; COSMIC: COSV65817768;