chr1-204160999-G-T

Position:

• chr1-204160999-G-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.373+293C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,166 control chromosomes in the GnomAD database, including 1,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1828 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.423

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=-0.92).
• BP6: Variant 1-204160999-G-T is Benign according to our data. Variant chr1-204160999-G-T is described in ClinVar as [Benign]. Clinvar id is 1272972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.373+293C>A		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.373+293C>A		intron_variant		1	NM_000537.4	ENSP00000272190	P1
REN	ENST00000638118.1	c.259+293C>A		intron_variant		5		ENSP00000490307

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23448 AN: 152048 Hom.: 1822 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23469 AN: 152166 Hom.: 1828 Cov.: 32 AF XY: 0.154 AC XY: 11476 AN XY: 74400

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.142

Alfa AF: 0.140 Hom.: 535

Bravo AF: 0.162

Asia WGS AF: 0.109 AC: 380 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

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.049
DANN	Benign	0.70

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: rs7521667; hg19: chr1-204130127;