rs10509549

Variant names:

• chr10-88455236-T-C
• rs10509549
• NM_001031709.3:c.527-92511A>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.527-92511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 150,286 control chromosomes in the GnomAD database, including 2,966 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 (2966 hom., cov: 31)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.527-92511A>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.527-92511A>G		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-92511A>G		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-92511A>G		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-92511A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27367 AN: 150170 Hom.: 2965 Cov.: 31

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00350

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.182 AC: 27371 AN: 150286 Hom.: 2966 Cov.: 31 AF XY: 0.177 AC XY: 12982 AN XY: 73364

African (AFR) AF: 0.0921 AC: 3711 AN: 40308

American (AMR) AF: 0.159 AC: 2398 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3456

East Asian (EAS) AF: 0.00351 AC: 18 AN: 5128

South Asian (SAS) AF: 0.0669 AC: 314 AN: 4692

European-Finnish (FIN) AF: 0.217 AC: 2266 AN: 10452

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

European-Non Finnish (NFE) AF: 0.259 AC: 17597 AN: 67832

Other (OTH) AF: 0.175 AC: 367 AN: 2094

Alfa AF: 0.227 Hom.: 13291

Bravo AF: 0.174

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		0.30
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: rs10509549; hg19: chr10-90214993;