10-88449581-C-T

Variant names:

• chr10-88449581-C-T
• rs11202748
• NM_001031709.3:c.527-86856G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031709.3(RNLS):​c.527-86856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,086 control chromosomes in the GnomAD database, including 2,401 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 0.17 (2401 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.527-86856G>A		intron	N/A	NP_001026879.2
	RNLS	NM_018363.4		c.527-86856G>A		intron	N/A	NP_060833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.527-86856G>A		intron	N/A	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.527-86856G>A		intron	N/A	ENSP00000361015.3
	RNLS	ENST00000466945.5	TSL:3	n.510-86856G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25359 AN: 151968 Hom.: 2388 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.167 AC: 25404 AN: 152086 Hom.: 2401 Cov.: 32 AF XY: 0.164 AC XY: 12204 AN XY: 74360

African (AFR) AF: 0.181 AC: 7513 AN: 41484

American (AMR) AF: 0.265 AC: 4053 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3466

East Asian (EAS) AF: 0.0920 AC: 476 AN: 5176

South Asian (SAS) AF: 0.207 AC: 998 AN: 4818

European-Finnish (FIN) AF: 0.0741 AC: 784 AN: 10576

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10173 AN: 67978

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.0988 Hom.: 178

Bravo AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11202748; hg19: chr10-90209338;