NM_001031709.3:c.527-89171C>T

Variant names:

• chr10-88451896-G-A
• rs10509546
• NM_001031709.3:c.527-89171C>T

Variant summary

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

The NM_001031709.3(RNLS):​c.527-89171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,274 control chromosomes in the GnomAD database, including 572 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 0.073 (572 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.527-89171C>T		intron_variant	Intron 4 of 6	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.527-89171C>T		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-89171C>T		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-89171C>T		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-89171C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11145 AN: 152156 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0732 AC: 11150 AN: 152274 Hom.: 572 Cov.: 32 AF XY: 0.0727 AC XY: 5412 AN XY: 74448

African (AFR) AF: 0.0174 AC: 724 AN: 41564

American (AMR) AF: 0.145 AC: 2213 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5184

South Asian (SAS) AF: 0.120 AC: 579 AN: 4820

European-Finnish (FIN) AF: 0.0575 AC: 610 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0911 AC: 6195 AN: 68012

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0815 Hom.: 80

Bravo AF: 0.0773

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.039
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: rs10509546; hg19: chr10-90211653;