NM_001031709.3:c.877-2446G>A

Variant names:

• chr10-88287952-C-T
• rs2162361
• NM_001031709.3:c.877-2446G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031709.3(RNLS):​c.877-2446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,018 control chromosomes in the GnomAD database, including 3,467 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 0.19 (3467 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.877-2446G>A		intron_variant	Intron 6 of 6	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.877-2446G>A		intron_variant	Intron 6 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.877-12920G>A		intron_variant	Intron 6 of 6	2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28761 AN: 151900 Hom.: 3461 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.189 AC: 28772 AN: 152018 Hom.: 3467 Cov.: 32 AF XY: 0.184 AC XY: 13663 AN XY: 74294

African (AFR) AF: 0.0482 AC: 2000 AN: 41514

American (AMR) AF: 0.232 AC: 3541 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3470

East Asian (EAS) AF: 0.133 AC: 688 AN: 5178

South Asian (SAS) AF: 0.117 AC: 562 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18444 AN: 67922

Other (OTH) AF: 0.185 AC: 391 AN: 2108

Alfa AF: 0.237 Hom.: 8673

Bravo AF: 0.189

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.72
PhyloP100		-0.82
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: rs2162361; hg19: chr10-90047709;