10-88275142-C-T

Position:

• chr10-88275142-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.877-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 816,896 control chromosomes in the GnomAD database, including 24,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4274 hom., cov: 32)
  • Exomes 𝑓: 0.25 (20522 hom.)
• Consequence: RNLS NM_018363.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830

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=-0.75).
• BP6: Variant 10-88275142-C-T is Benign according to our data. Variant chr10-88275142-C-T is described in ClinVar as [Benign]. Clinvar id is 1257899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_018363.4	c.877-110G>A		intron_variant			NP_060833.1
RNLS	XM_011539924.4	c.877-110G>A		intron_variant			XP_011538226.1
RNLS	XM_017016380.3	c.877-110G>A		intron_variant			XP_016871869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000371947.7	c.877-110G>A		intron_variant		2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35782 AN: 151826 Hom.: 4265 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.245 AC: 163147 AN: 664954 Hom.: 20522 AF XY: 0.247 AC XY: 86189 AN XY: 348424

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.236 AC: 35833 AN: 151942 Hom.: 4274 Cov.: 32 AF XY: 0.234 AC XY: 17357 AN XY: 74260

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.238

Alfa AF: 0.244 Hom.: 699

Bravo AF: 0.234

Asia WGS AF: 0.278 AC: 966 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	-0.75
CADD	Benign	9.0
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45585838; hg19: chr10-90034899; COSMIC: COSV64263085;