10-88518623-A-C

Variant names:

• chr10-88518623-A-C
• rs2437871
• NM_001031709.3:c.526+54280T>G

Variant summary

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

The NM_001031709.3(RNLS):​c.526+54280T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,116 control chromosomes in the GnomAD database, including 15,056 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 0.44 (15056 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 7 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

ENSG00000293705 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.526+54280T>G		intron_variant	Intron 4 of 6	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.526+54280T>G		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66659 AN: 150998 Hom.: 15043 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.441 AC: 66710 AN: 151116 Hom.: 15056 Cov.: 32 AF XY: 0.442 AC XY: 32613 AN XY: 73834

African (AFR) AF: 0.333 AC: 13586 AN: 40824

American (AMR) AF: 0.510 AC: 7737 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3464

East Asian (EAS) AF: 0.588 AC: 3032 AN: 5158

South Asian (SAS) AF: 0.474 AC: 2279 AN: 4810

European-Finnish (FIN) AF: 0.430 AC: 4559 AN: 10596

Middle Eastern (MID) AF: 0.517 AC: 149 AN: 288

European-Non Finnish (NFE) AF: 0.475 AC: 32177 AN: 67804

Other (OTH) AF: 0.464 AC: 973 AN: 2098

Alfa AF: 0.434 Hom.: 4662

Bravo AF: 0.441

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.042
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: rs2437871; hg19: chr10-90278380;