chr1-204167500-C-T

Variant names:

• chr1-204167500-C-T
• rs6681776
• ENST00000638118.1:c.-17+5007G>A

Variant summary

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

The ENST00000638118.1(REN):​c.-17+5007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,202 control chromosomes in the GnomAD database, including 1,622 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 0.14 (1622 hom., cov: 32)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 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.-17+5007G>A		intron_variant	Intron 3 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21622 AN: 152084 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.142 AC: 21644 AN: 152202 Hom.: 1622 Cov.: 32 AF XY: 0.140 AC XY: 10384 AN XY: 74424

African (AFR) AF: 0.186 AC: 7716 AN: 41516

American (AMR) AF: 0.109 AC: 1664 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.113 AC: 587 AN: 5182

South Asian (SAS) AF: 0.153 AC: 737 AN: 4824

European-Finnish (FIN) AF: 0.0985 AC: 1044 AN: 10604

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8916 AN: 67994

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.136 Hom.: 6006

Bravo AF: 0.143

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.51
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs6681776; hg19: chr1-204136628;