1-204157117-A-T

Position:

• chr1-204157117-A-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.698+244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,218 control chromosomes in the GnomAD database, including 31 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 0.016 (31 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2380/152218) while in subpopulation NFE AF= 0.0263 (1790/67996). AF 95% confidence interval is 0.0253. There are 31 homozygotes in gnomad4. There are 1098 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2380 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REN	NM_000537.4	c.698+244T>A		intron_variant		ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.698+244T>A		intron_variant		1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.584+244T>A		intron_variant		5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2379 AN: 152100 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0156 AC: 2380 AN: 152218 Hom.: 31 Cov.: 32 AF XY: 0.0148 AC XY: 1098 AN XY: 74428

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00765 Hom.: 0

Bravo AF: 0.0147

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	-0.90
CADD	Benign	0.19
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11571087; hg19: chr1-204126245;