10-88275126-C-T

Position:

• chr10-88275126-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018363.4(RNLS):​c.877-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 973,534 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (181 hom., cov: 32)
  • Exomes 𝑓: 0.029 (487 hom.)
• Consequence: RNLS NM_018363.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.642

Genes affected

RNLS (HGNC:25641): (renalase, FAD dependent amine oxidase) Enables several functions, including NADH binding activity; epinephrine binding activity; and monoamine oxidase activity. Involved in negative regulation of blood pressure and negative regulation of heart rate. Located in extracellular region. Implicated in essential hypertension and hypertension. Biomarker of end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

RNLS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-88275126-C-T is Benign according to our data. Variant chr10-88275126-C-T is described in ClinVar as [Benign]. Clinvar id is 1264620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_018363.4	c.877-94G>A		intron_variant			NP_060833.1
RNLS	XM_011539924.4	c.877-94G>A		intron_variant			XP_011538226.1
RNLS	XM_017016380.3	c.877-94G>A		intron_variant			XP_016871869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000371947.7	c.877-94G>A		intron_variant		2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6428 AN: 152044 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00623

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.0295 AC: 24194 AN: 821372 Hom.: 487 AF XY: 0.0285 AC XY: 12238 AN XY: 429392

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0441

Gnomad4 EAS exome AF: 0.000582

Gnomad4 SAS exome AF: 0.00764

Gnomad4 FIN exome AF: 0.00795

Gnomad4 NFE exome AF: 0.0334

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.0425 AC: 6460 AN: 152162 Hom.: 181 Cov.: 32 AF XY: 0.0392 AC XY: 2919 AN XY: 74378

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.00623

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0446 Hom.: 32

Bravo AF: 0.0473

Asia WGS AF: 0.0320 AC: 111 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72818071; hg19: chr10-90034883;