1-204155737-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000537.4(REN):c.1059+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,044,162 control chromosomes in the GnomAD database, including 49,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (13063 hom., cov: 32)
  • Exomes 𝑓: 0.28 (36744 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-204155737-C-T is Benign according to our data. Variant chr1-204155737-C-T is described in ClinVar as [Benign]. Clinvar id is 1239591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.1059+83G>A		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.1059+83G>A		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.945+83G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57088 AN: 151912 Hom.: 13021 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.275 AC: 245489 AN: 892132 Hom.: 36744 AF XY: 0.275 AC XY: 126577 AN XY: 461042

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.269

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.376 AC: 57174 AN: 152030 Hom.: 13063 Cov.: 32 AF XY: 0.371 AC XY: 27554 AN XY: 74352

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.350

Alfa AF: 0.278 Hom.: 2952

Bravo AF: 0.395

Asia WGS AF: 0.241 AC: 843 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.61
Dann	Benign	0.79

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: rs2368564; hg19: chr1-204124865; COSMIC: COSV65817911; COSMIC: COSV65817911;