rs12220927

Variant names:

• chr10-88230790-T-G
• rs12220927
• XM_011539924.4:c.*28+44143A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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

LOC101929727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNLS	XM_011539924.4	c.*28+44143A>C		intron_variant	Intron 7 of 7		XP_011538226.1
RNLS	XM_017016382.3	c.*28+44143A>C		intron_variant	Intron 5 of 5		XP_016871871.1
RNLS	XR_001747122.3	n.1104+44143A>C		intron_variant	Intron 7 of 8
LOC101929727	XR_001747537.3	n.442+98237T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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

African (AFR) AF: 0.0866 AC: 3601 AN: 41568

American (AMR) AF: 0.119 AC: 1820 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3468

East Asian (EAS) AF: 0.00847 AC: 44 AN: 5192

South Asian (SAS) AF: 0.215 AC: 1038 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10608

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11251 AN: 68028

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.157 Hom.: 3340

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
PhyloP100		-0.024

Splicing

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

Other links and lift over

dbSNP: rs12220927; hg19: chr10-89990547;