1-204155961-G-A

Position:

• chr1-204155961-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.961-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,542,266 control chromosomes in the GnomAD database, including 14,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1585 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12454 hom.)
• Consequence: REN ENST00000272190.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.267

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=-0.93).
• BP6: Variant 1-204155961-G-A is Benign according to our data. Variant chr1-204155961-G-A is described in ClinVar as [Benign]. Clinvar id is 1236555.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.961-43C>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.961-43C>T		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.847-43C>T		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21918 AN: 152030 Hom.: 1581 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.139 AC: 34228 AN: 246470 Hom.: 2472 AF XY: 0.136 AC XY: 18206 AN XY: 133618

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.0732

Gnomad SAS exome AF: 0.0990

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.131 AC: 181683 AN: 1390118 Hom.: 12454 Cov.: 22 AF XY: 0.130 AC XY: 90594 AN XY: 695782

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.0859

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.144 AC: 21933 AN: 152148 Hom.: 1585 Cov.: 32 AF XY: 0.143 AC XY: 10663 AN XY: 74394

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0774

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.135

Alfa AF: 0.129 Hom.: 1296

Bravo AF: 0.150

Asia WGS AF: 0.100 AC: 352 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.93
CADD	Benign	1.2
DANN	Benign	0.58

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: rs3795575; hg19: chr1-204125089;