rs2368564

Variant names:

• chr1-204155737-C-T
• rs2368564
• NM_000537.4:c.1059+83G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-204155737-C-T
• chr1-204155737-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 33 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• renal tubular dysgenesis of genetic origin

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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1239591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 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.1059+83G>A		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.1059+83G>A		intron	N/A	ENSP00000272190.8	P00797-1
	REN	ENST00000851325.1		c.1050+83G>A		intron	N/A	ENSP00000521384.1
	REN	ENST00000638118.1	TSL:5	c.945+83G>A		intron	N/A	ENSP00000490307.1	A0A1B0GUZ2

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

African (AFR) AF: 0.678 AC: 15341 AN: 22612

American (AMR) AF: 0.296 AC: 10511 AN: 35534

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 6578 AN: 21982

East Asian (EAS) AF: 0.193 AC: 6747 AN: 35004

South Asian (SAS) AF: 0.269 AC: 18774 AN: 69742

European-Finnish (FIN) AF: 0.264 AC: 12328 AN: 46672

Middle Eastern (MID) AF: 0.398 AC: 1886 AN: 4734

European-Non Finnish (NFE) AF: 0.262 AC: 160988 AN: 614356

Other (OTH) AF: 0.297 AC: 12336 AN: 41496

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

African (AFR) AF: 0.659 AC: 27328 AN: 41440

American (AMR) AF: 0.310 AC: 4736 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3472

East Asian (EAS) AF: 0.189 AC: 978 AN: 5162

South Asian (SAS) AF: 0.246 AC: 1181 AN: 4806

European-Finnish (FIN) AF: 0.260 AC: 2759 AN: 10596

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18041 AN: 67976

Other (OTH) AF: 0.350 AC: 736 AN: 2104

Alfa AF: 0.303 Hom.: 17263

Bravo AF: 0.395

Asia WGS AF: 0.241 AC: 843 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.61
DANN	Benign	0.79
PhyloP100		-1.4
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: rs2368564; hg19: chr1-204124865; COSMIC: COSV65817911; COSMIC: COSV65817911;