NM_001031709.3:c.527-86856G>C

Variant names:

• chr10-88449581-C-G
• rs11202748
• NM_001031709.3:c.527-86856G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001031709.3(RNLS):​c.527-86856G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 152,120 control chromosomes in the GnomAD database, including 22 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 0.0085 (22 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 5 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=-0.67).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00851 (1294/152120) while in subpopulation EAS AF = 0.0328 (170/5178). AF 95% confidence interval is 0.0288. There are 22 homozygotes in GnomAd4. There are 835 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.527-86856G>C		intron	N/A	NP_001026879.2
	RNLS	NM_018363.4		c.527-86856G>C		intron	N/A	NP_060833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.527-86856G>C		intron	N/A	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.527-86856G>C		intron	N/A	ENSP00000361015.3
	RNLS	ENST00000466945.5	TSL:3	n.510-86856G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00853 AC: 1296 AN: 152002 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.00851 AC: 1294 AN: 152120 Hom.: 22 Cov.: 32 AF XY: 0.0112 AC XY: 835 AN XY: 74384

African (AFR) AF: 0.000603 AC: 25 AN: 41490

American (AMR) AF: 0.00609 AC: 93 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5178

South Asian (SAS) AF: 0.0183 AC: 88 AN: 4820

European-Finnish (FIN) AF: 0.0513 AC: 543 AN: 10576

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00421 AC: 286 AN: 67990

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00472 Hom.: 178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.022
Mutation Taster		=100/0	polymorphism

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: rs11202748; hg19: chr10-90209338;