rs10509548

Variant names:

• chr10-88453705-C-T
• rs10509548
• NM_001031709.3:c.527-90980G>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.527-90980G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,154 control chromosomes in the GnomAD database, including 3,028 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 0.19 (3028 hom., cov: 33)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.527-90980G>A		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.527-90980G>A		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-90980G>A		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-90980G>A		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-90980G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28311 AN: 152036 Hom.: 3027 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.186 AC: 28324 AN: 152154 Hom.: 3028 Cov.: 33 AF XY: 0.180 AC XY: 13416 AN XY: 74374

African (AFR) AF: 0.117 AC: 4872 AN: 41512

American (AMR) AF: 0.159 AC: 2432 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4828

European-Finnish (FIN) AF: 0.213 AC: 2248 AN: 10560

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17349 AN: 67990

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.202 Hom.: 574

Bravo AF: 0.180

Asia WGS AF: 0.0470 AC: 163 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	3.3
DANN	Benign	0.44
PhyloP100		-0.66
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: rs10509548; hg19: chr10-90213462;