chr1-204179949-C-G

Variant names:

• chr1-204179949-C-G
• rs11240692
• ENST00000638118.1:c.-210-6029G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638118.1(REN):​c.-210-6029G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,988 control chromosomes in the GnomAD database, including 19,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19062 hom., cov: 31)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000638118.1	c.-210-6029G>C		intron_variant	Intron 1 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72182 AN: 151870 Hom.: 19019 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.476 AC: 72287 AN: 151988 Hom.: 19062 Cov.: 31 AF XY: 0.471 AC XY: 35023 AN XY: 74282

African (AFR) AF: 0.725 AC: 30064 AN: 41460

American (AMR) AF: 0.425 AC: 6490 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1314 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2478 AN: 5148

South Asian (SAS) AF: 0.312 AC: 1499 AN: 4804

European-Finnish (FIN) AF: 0.374 AC: 3949 AN: 10566

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.370 AC: 25151 AN: 67948

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.252 Hom.: 532

Bravo AF: 0.494

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.085
DANN	Benign	0.51
PhyloP100		-0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11240692; hg19: chr1-204149077;