chr1-204159726-T-G

Position:

• chr1-204159726-T-G

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.493-131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 759,204 control chromosomes in the GnomAD database, including 168,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33308 hom., cov: 31)
  • Exomes 𝑓: 0.67 (135500 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0670

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=-0.87).
• BP6: Variant 1-204159726-T-G is Benign according to our data. Variant chr1-204159726-T-G is described in ClinVar as [Benign]. Clinvar id is 1249555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.493-131A>C		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.493-131A>C		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.379-131A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100474 AN: 151848 Hom.: 33274 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.666 AC: 404416 AN: 607238 Hom.: 135500 AF XY: 0.670 AC XY: 218476 AN XY: 326094

Gnomad4 AFR exome AF: 0.660

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.740

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.662 AC: 100562 AN: 151966 Hom.: 33308 Cov.: 31 AF XY: 0.664 AC XY: 49346 AN XY: 74268

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.680

Alfa AF: 0.639 Hom.: 15662

Bravo AF: 0.665

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.49

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: rs1464816; hg19: chr1-204128854;