10-88521181-T-C

Variant names:

• chr10-88521181-T-C
• rs1325904
• NM_001031709.3:c.526+51722A>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+51722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 151,954 control chromosomes in the GnomAD database, including 51,144 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 0.82 (51144 hom., cov: 31)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 3 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

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 = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.526+51722A>G		intron	N/A	NP_001026879.2	Q5VYX0-1
	RNLS	NM_018363.4		c.526+51722A>G		intron	N/A	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.526+51722A>G		intron	N/A	ENSP00000332530.4	Q5VYX0-1
	RNLS	ENST00000371947.7	TSL:2	c.526+51722A>G		intron	N/A	ENSP00000361015.3	Q5VYX0-2
	RNLS	ENST00000466945.5	TSL:3	n.509+60386A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124001 AN: 151836 Hom.: 51088 Cov.: 31

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.817 AC: 124115 AN: 151954 Hom.: 51144 Cov.: 31 AF XY: 0.823 AC XY: 61135 AN XY: 74300

African (AFR) AF: 0.907 AC: 37636 AN: 41480

American (AMR) AF: 0.831 AC: 12656 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2953 AN: 3462

East Asian (EAS) AF: 0.996 AC: 5151 AN: 5174

South Asian (SAS) AF: 0.863 AC: 4157 AN: 4818

European-Finnish (FIN) AF: 0.822 AC: 8702 AN: 10584

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50193 AN: 67900

Other (OTH) AF: 0.821 AC: 1730 AN: 2108

Alfa AF: 0.765 Hom.: 56800

Bravo AF: 0.821

Asia WGS AF: 0.939 AC: 3264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.97
DANN	Benign	0.48
PhyloP100		-0.23
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: rs1325904; hg19: chr10-90280938;