rs6676670

Variant names:

• chr1-204163688-G-A
• rs6676670
• NM_000537.4:c.99-1525C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204163688-G-A
• chr1-204163688-G-C
• chr1-204163688-G-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.99-1525C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 152,006 control chromosomes in the GnomAD database, including 5 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 0.0030 (5 hom., cov: 32)
• Consequence: REN NM_000537.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00299 (454/152006) while in subpopulation EAS AF = 0.0409 (211/5158). AF 95% confidence interval is 0.0364. There are 5 homozygotes in GnomAd4. There are 272 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REN	NM_000537.4	c.99-1525C>T		intron_variant	Intron 1 of 9	ENST00000272190.9	NP_000528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REN	ENST00000272190.9	c.99-1525C>T		intron_variant	Intron 1 of 9	1	NM_000537.4	ENSP00000272190.8
REN	ENST00000638118.1	c.-16-1525C>T		intron_variant	Intron 3 of 11	5		ENSP00000490307.1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 151888 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00606

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00144

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

GnomAD4 genome AF: 0.00299 AC: 454 AN: 152006 Hom.: 5 Cov.: 32 AF XY: 0.00366 AC XY: 272 AN XY: 74288

Gnomad4 AFR AF: 0.0000483 AC: 0.0000482532 AN: 0.0000482532

Gnomad4 AMR AF: 0.00858 AC: 0.00857554 AN: 0.00857554

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0409 AC: 0.0409073 AN: 0.0409073

Gnomad4 SAS AF: 0.00249 AC: 0.00249273 AN: 0.00249273

Gnomad4 FIN AF: 0.00606 AC: 0.0060629 AN: 0.0060629

Gnomad4 NFE AF: 0.000456 AC: 0.000456097 AN: 0.000456097

Gnomad4 OTH AF: 0.00142 AC: 0.00142315 AN: 0.00142315

Alfa AF: 0.0000414 Hom.: 7074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.93
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

Publications

LitVar

Other links and lift over

dbSNP: rs6676670; hg19: chr1-204132816; COSMIC: COSV65818217;