1-204155417-A-G

Variant names:

• chr1-204155417-A-G
• rs11571091
• NM_000537.4:c.1060-240T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

REN Gene-Disease associations (from GenCC):

• familial juvenile hyperuricemic nephropathy type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000537.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REN	NM_000537.4	MANE Select	c.1060-240T>C		intron	N/A	NP_000528.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REN	ENST00000272190.9	TSL:1 MANE Select	c.1060-240T>C		intron	N/A	ENSP00000272190.8
	REN	ENST00000638118.1	TSL:5	c.946-240T>C		intron	N/A	ENSP00000490307.1

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

African (AFR) AF: 0.166 AC: 6908 AN: 41534

American (AMR) AF: 0.172 AC: 2627 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3472

East Asian (EAS) AF: 0.0788 AC: 408 AN: 5178

South Asian (SAS) AF: 0.103 AC: 496 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1788 AN: 10608

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9955 AN: 67998

Other (OTH) AF: 0.145 AC: 306 AN: 2114

Alfa AF: 0.146 Hom.: 819

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

Jun 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.47
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11571091; hg19: chr1-204124545;