chr1-204161903-C-T

Variant names:

• chr1-204161903-C-T
• rs11571082
• NM_000537.4:c.249+110G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000537.4(REN):​c.249+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,392,112 control chromosomes in the GnomAD database, including 12,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2312 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10448 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.326
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-204161903-C-T is Benign according to our data. Variant chr1-204161903-C-T is described in ClinVar as Benign. ClinVar VariationId is 1223960.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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
REN	NM_000537.4	c.249+110G>A		intron_variant	Intron 2 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.249+110G>A		intron_variant	Intron 2 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.135+110G>A		intron_variant	Intron 4 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25129 AN: 151876 Hom.: 2303 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.125 AC: 154619 AN: 1240118 Hom.: 10448 AF XY: 0.125 AC XY: 76922 AN XY: 617692

African (AFR) AF: 0.275 AC: 7890 AN: 28660

American (AMR) AF: 0.174 AC: 6528 AN: 37524

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 3453 AN: 21766

East Asian (EAS) AF: 0.0681 AC: 2560 AN: 37570

South Asian (SAS) AF: 0.113 AC: 8244 AN: 73024

European-Finnish (FIN) AF: 0.111 AC: 5570 AN: 50286

Middle Eastern (MID) AF: 0.179 AC: 684 AN: 3826

European-Non Finnish (NFE) AF: 0.121 AC: 112689 AN: 935052

Other (OTH) AF: 0.134 AC: 7001 AN: 52410

GnomAD4 genome AF: 0.166 AC: 25175 AN: 151994 Hom.: 2312 Cov.: 31 AF XY: 0.164 AC XY: 12195 AN XY: 74304

African (AFR) AF: 0.266 AC: 11032 AN: 41442

American (AMR) AF: 0.166 AC: 2534 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3470

East Asian (EAS) AF: 0.0670 AC: 346 AN: 5168

South Asian (SAS) AF: 0.108 AC: 519 AN: 4804

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10604

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8598 AN: 67930

Other (OTH) AF: 0.153 AC: 322 AN: 2102

Alfa AF: 0.167 Hom.: 451

Bravo AF: 0.176

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11571082; hg19: chr1-204131031;