1-204157289-G-T

Variant names:

• chr1-204157289-G-T
• rs3730101
• NM_000537.4:c.698+72C>A

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.698+72C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 1,594,504 control chromosomes in the GnomAD database, including 56 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 0.0055 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0072 (50 hom.)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• 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, 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=-0.94).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00552 (841/152310) while in subpopulation AMR AF = 0.00922 (141/15298). AF 95% confidence interval is 0.00798. There are 6 homozygotes in GnomAd4. There are 405 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.698+72C>A		intron_variant	Intron 6 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.698+72C>A		intron_variant	Intron 6 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.584+72C>A		intron_variant	Intron 8 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152192 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00807

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00718 AC: 10356 AN: 1442194 Hom.: 50 AF XY: 0.00709 AC XY: 5095 AN XY: 718682

African (AFR) AF: 0.00154 AC: 51 AN: 33076

American (AMR) AF: 0.00707 AC: 316 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00400 AC: 104 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85860

European-Finnish (FIN) AF: 0.00562 AC: 300 AN: 53410

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5706

European-Non Finnish (NFE) AF: 0.00844 AC: 9233 AN: 1094110

Other (OTH) AF: 0.00552 AC: 330 AN: 59732

GnomAD4 genome AF: 0.00552 AC: 841 AN: 152310 Hom.: 6 Cov.: 33 AF XY: 0.00544 AC XY: 405 AN XY: 74480

African (AFR) AF: 0.00159 AC: 66 AN: 41578

American (AMR) AF: 0.00922 AC: 141 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00621 AC: 66 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00807 AC: 549 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.000802 Hom.: 0

Bravo AF: 0.00536

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0020
DANN	Benign	0.70
PhyloP100		-3.0
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: rs3730101; hg19: chr1-204126417;