rs10509550

Variant names:

• chr10-88459541-T-C
• rs10509550
• NM_001031709.3:c.527-96816A>G

Variant summary

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

The NM_001031709.3(RNLS):​c.527-96816A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,106 control chromosomes in the GnomAD database, including 2,970 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 0.18 (2970 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 7 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=-0.91).
• 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.527-96816A>G		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.527-96816A>G		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-96816A>G		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-96816A>G		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-96816A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27893 AN: 151988 Hom.: 2969 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.183 AC: 27906 AN: 152106 Hom.: 2970 Cov.: 32 AF XY: 0.178 AC XY: 13252 AN XY: 74364

African (AFR) AF: 0.108 AC: 4486 AN: 41500

American (AMR) AF: 0.159 AC: 2432 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5182

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2252 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17326 AN: 67966

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.231 Hom.: 6895

Bravo AF: 0.177

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.22
PhyloP100		0.034
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: rs10509550; hg19: chr10-90219298;