rs12220927

Positions:

• chr10-88230790-T-G

Variant summary

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

The XM_011539924.4(RNLS):​c.*28+44143A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,308 control chromosomes in the GnomAD database, including 1,527 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 0.13 (1527 hom., cov: 34)
• Consequence: RNLS XM_011539924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	XM_011539924.4	c.*28+44143A>C		intron_variant			XP_011538226.1
RNLS	XM_017016382.3	c.*28+44143A>C		intron_variant			XP_016871871.1
		n.88230790T>G		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20308 AN: 152190 Hom.: 1530 Cov.: 34

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.133 AC: 20309 AN: 152308 Hom.: 1527 Cov.: 34 AF XY: 0.130 AC XY: 9693 AN XY: 74474

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.00847

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.160

Alfa AF: 0.161 Hom.: 2757

Bravo AF: 0.126

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12220927; hg19: chr10-89990547;