rs2368564

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000537.4(REN):​c.1059+83G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,045,830 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00233 (354/152084) while in subpopulation AFR AF = 0.00789 (327/41464). AF 95% confidence interval is 0.00718. There are 2 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.1059+83G>C		intron_variant	Intron 9 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.1059+83G>C		intron_variant	Intron 9 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.945+83G>C		intron_variant	Intron 11 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 353 AN: 151966 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000264 AC: 236 AN: 893746 Hom.: 1 AF XY: 0.000240 AC XY: 111 AN XY: 461834

African (AFR) AF: 0.00786 AC: 178 AN: 22644

American (AMR) AF: 0.000563 AC: 20 AN: 35546

Ashkenazi Jewish (ASJ) AF: 0.000182 AC: 4 AN: 22006

East Asian (EAS) AF: 0.0000286 AC: 1 AN: 35018

South Asian (SAS) AF: 0.00 AC: 0 AN: 69770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46722

Middle Eastern (MID) AF: 0.000422 AC: 2 AN: 4736

European-Non Finnish (NFE) AF: 0.0000260 AC: 16 AN: 615762

Other (OTH) AF: 0.000361 AC: 15 AN: 41542

GnomAD4 genome AF: 0.00233 AC: 354 AN: 152084 Hom.: 2 Cov.: 32 AF XY: 0.00223 AC XY: 166 AN XY: 74382

African (AFR) AF: 0.00789 AC: 327 AN: 41464

American (AMR) AF: 0.00124 AC: 19 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00 Hom.: 17263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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;