chr1-204155242-AC-A

Variant names:

• chr1-204155242-AC-A
• rs3215332
• NM_000537.4:c.1060-66delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000537.4(REN):​c.1060-66delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,568,114 control chromosomes in the GnomAD database, including 34,508 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3576 hom., cov: 27)
  • Exomes 𝑓: 0.21 (30932 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.514
• Publications: 2 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, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-204155242-AC-A is Benign according to our data. Variant chr1-204155242-AC-A is described in ClinVar as Benign. ClinVar VariationId is 1177782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000537.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REN	NM_000537.4	MANE Select	c.1060-66delG		intron	N/A	NP_000528.1	P00797-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REN	ENST00000272190.9	TSL:1 MANE Select	c.1060-66delG		intron	N/A	ENSP00000272190.8	P00797-1
	REN	ENST00000851325.1		c.1051-66delG		intron	N/A	ENSP00000521384.1
	REN	ENST00000638118.1	TSL:5	c.946-66delG		intron	N/A	ENSP00000490307.1	A0A1B0GUZ2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33270 AN: 151228 Hom.: 3573 Cov.: 27

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.207 AC: 292602 AN: 1416768 Hom.: 30932 AF XY: 0.208 AC XY: 147055 AN XY: 707546

African (AFR) AF: 0.241 AC: 7843 AN: 32492

American (AMR) AF: 0.238 AC: 10569 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7085 AN: 25812

East Asian (EAS) AF: 0.193 AC: 7602 AN: 39460

South Asian (SAS) AF: 0.224 AC: 19008 AN: 85002

European-Finnish (FIN) AF: 0.210 AC: 11027 AN: 52492

Middle Eastern (MID) AF: 0.314 AC: 1758 AN: 5590

European-Non Finnish (NFE) AF: 0.201 AC: 215209 AN: 1072588

Other (OTH) AF: 0.212 AC: 12501 AN: 58854

GnomAD4 genome AF: 0.220 AC: 33293 AN: 151346 Hom.: 3576 Cov.: 27 AF XY: 0.219 AC XY: 16171 AN XY: 73910

African (AFR) AF: 0.236 AC: 9719 AN: 41160

American (AMR) AF: 0.226 AC: 3438 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1002 AN: 3458

East Asian (EAS) AF: 0.190 AC: 972 AN: 5118

South Asian (SAS) AF: 0.210 AC: 1002 AN: 4776

European-Finnish (FIN) AF: 0.211 AC: 2214 AN: 10480

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14212 AN: 67820

Other (OTH) AF: 0.219 AC: 461 AN: 2104

Alfa AF: 0.216 Hom.: 359

Bravo AF: 0.222

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3215332; hg19: chr1-204124370; COSMIC: COSV107237460; COSMIC: COSV107237460;