1-204155417-A-G

Position:

• chr1-204155417-A-G

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.1060-240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,226 control chromosomes in the GnomAD database, including 1,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1793 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.942

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=-0.9).
• BP6: Variant 1-204155417-A-G is Benign according to our data. Variant chr1-204155417-A-G is described in ClinVar as [Benign]. Clinvar id is 1281982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.1060-240T>C		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.1060-240T>C		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.946-240T>C		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23314 AN: 152108 Hom.: 1789 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23328 AN: 152226 Hom.: 1793 Cov.: 32 AF XY: 0.153 AC XY: 11398 AN XY: 74448

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.145

Alfa AF: 0.146 Hom.: 496

Bravo AF: 0.157

Asia WGS AF: 0.105 AC: 367 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

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.47

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: rs11571091; hg19: chr1-204124545;