rs10749571

Positions:

• chr10-88284588-A-G
• chr10-88284588-A-T

Variant summary

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

The NM_001031709.3(RNLS):​c.*766T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 985,022 control chromosomes in the GnomAD database, including 389,770 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 0.87 (57602 hom., cov: 33)
  • Exomes 𝑓: 0.89 (332168 hom.)
• Consequence: RNLS NM_001031709.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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 (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 = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.*766T>C		3_prime_UTR_variant	7/7	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772	c.*766T>C		3_prime_UTR_variant	7/7	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.877-9556T>C		intron_variant		2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132161 AN: 152056 Hom.: 57551 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.865

GnomAD4 exome AF: 0.893 AC: 743712 AN: 832848 Hom.: 332168 Cov.: 27 AF XY: 0.894 AC XY: 343802 AN XY: 384598

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.825

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.899

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.881

GnomAD4 genome AF: 0.869 AC: 132273 AN: 152174 Hom.: 57602 Cov.: 33 AF XY: 0.870 AC XY: 64722 AN XY: 74388

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.917

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.864

Alfa AF: 0.881 Hom.: 80452

Bravo AF: 0.864

Asia WGS AF: 0.852 AC: 2961 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	0.52
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10749571; hg19: chr10-90044345;