1-204163182-A-G

Position:

• chr1-204163182-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000537.4(REN):​c.99-1019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,858 control chromosomes in the GnomAD database, including 13,818 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 0.42 (13818 hom., cov: 31)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.99-1019T>C		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.99-1019T>C		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.-16-1019T>C		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63212 AN: 151740 Hom.: 13797 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.417 AC: 63286 AN: 151858 Hom.: 13818 Cov.: 31 AF XY: 0.416 AC XY: 30907 AN XY: 74214

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.396

Alfa AF: 0.346 Hom.: 7463

Bravo AF: 0.431

Asia WGS AF: 0.418 AC: 1452 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	9.0
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10900555; hg19: chr1-204132310;