chr1-204162503-T-C

Variant names:

• chr1-204162503-T-C
• rs11571080
• NM_000537.4:c.99-340A>G

Variant summary

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

The NM_000537.4(REN):​c.99-340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,114 control chromosomes in the GnomAD database, including 12,647 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 0.39 (12647 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.99-340A>G		intron_variant	Intron 1 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.99-340A>G		intron_variant	Intron 1 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.-16-340A>G		intron_variant	Intron 3 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59810 AN: 151994 Hom.: 12627 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.394 AC: 59884 AN: 152114 Hom.: 12647 Cov.: 32 AF XY: 0.394 AC XY: 29308 AN XY: 74354

African (AFR) AF: 0.547 AC: 22706 AN: 41474

American (AMR) AF: 0.401 AC: 6134 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2622 AN: 5174

South Asian (SAS) AF: 0.284 AC: 1372 AN: 4830

European-Finnish (FIN) AF: 0.331 AC: 3511 AN: 10594

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21229 AN: 67986

Other (OTH) AF: 0.368 AC: 774 AN: 2102

Alfa AF: 0.339 Hom.: 23309

Bravo AF: 0.408

Asia WGS AF: 0.406 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11571080; hg19: chr1-204131631;