rs11240695

Variant names:

• chr1-204189004-C-A
• rs11240695
• ENST00000638118.1:c.-211+1228G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204189004-C-A
• chr1-204189004-C-G

Variant summary

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

The ENST00000638118.1(REN):​c.-211+1228G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,998 control chromosomes in the GnomAD database, including 6,669 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 0.29 (6669 hom., cov: 31)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 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.-211+1228G>T		intron_variant	Intron 1 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44130 AN: 151880 Hom.: 6660 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.291 AC: 44173 AN: 151998 Hom.: 6669 Cov.: 31 AF XY: 0.289 AC XY: 21481 AN XY: 74290

African (AFR) AF: 0.348 AC: 14397 AN: 41424

American (AMR) AF: 0.319 AC: 4877 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2290 AN: 5156

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2341 AN: 10586

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17097 AN: 67960

Other (OTH) AF: 0.293 AC: 618 AN: 2108

Alfa AF: 0.268 Hom.: 21931

Bravo AF: 0.302

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs11240695; hg19: chr1-204158132;