rs2368564

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 354 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REN	NM_000537.4	c.1059+83G>C		intron_variant		ENST00000272190.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REN	ENST00000272190.9	c.1059+83G>C		intron_variant		1	NM_000537.4	P1
REN	ENST00000638118.1	c.945+83G>C		intron_variant		5

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

Gnomad4 AFR exome AF: 0.00786

Gnomad4 AMR exome AF: 0.000563

Gnomad4 ASJ exome AF: 0.000182

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000260

Gnomad4 OTH exome AF: 0.000361

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

Gnomad4 AFR AF: 0.00789

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00143

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2368564; hg19: chr1-204124865;