rs10509540

Positions:

• chr10-88263276-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017016380.3(RNLS):​c.*2759A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,988 control chromosomes in the GnomAD database, including 4,893 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 0.25 (4893 hom., cov: 31)
• Consequence: RNLS XM_017016380.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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]

LOC101929727 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	XM_017016380.3	c.*2759A>G		3_prime_UTR_variant	8/8		XP_016871869.1
RNLS	XM_011539924.4	c.*28+11657A>G		intron_variant			XP_011538226.1
RNLS	XM_017016382.3	c.*28+11657A>G		intron_variant			XP_016871871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38461 AN: 151866 Hom.: 4889 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.253 AC: 38485 AN: 151988 Hom.: 4893 Cov.: 31 AF XY: 0.255 AC XY: 18933 AN XY: 74306

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.253

Alfa AF: 0.264 Hom.: 10653

Bravo AF: 0.252

Asia WGS AF: 0.307 AC: 1070 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10509540; hg19: chr10-90023033;