rs41317140

Variant names:

• chr1-204170358-G-A
• rs41317140
• ENST00000638118.1:c.-17+2149C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204170358-G-A
• chr1-204170358-G-C

Variant summary

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

The ENST00000638118.1(REN):​c.-17+2149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,140 control chromosomes in the GnomAD database, including 2,363 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 0.17 (2363 hom., cov: 32)
• Consequence: REN ENST00000638118.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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+2149C>T		intron_variant	Intron 3 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25159 AN: 152022 Hom.: 2356 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.166 AC: 25189 AN: 152140 Hom.: 2363 Cov.: 32 AF XY: 0.162 AC XY: 12066 AN XY: 74378

African (AFR) AF: 0.266 AC: 11025 AN: 41490

American (AMR) AF: 0.117 AC: 1791 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3472

East Asian (EAS) AF: 0.114 AC: 589 AN: 5176

South Asian (SAS) AF: 0.152 AC: 734 AN: 4818

European-Finnish (FIN) AF: 0.0986 AC: 1043 AN: 10580

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8964 AN: 68006

Other (OTH) AF: 0.173 AC: 366 AN: 2112

Alfa AF: 0.0900 Hom.: 142

Bravo AF: 0.170

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.53
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs41317140; hg19: chr1-204139486;