rs74146690

Variant names:

• chr10-88285755-G-A
• rs74146690
• NM_001031709.3:c.877-249C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001031709.3(RNLS):​c.877-249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 152,094 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (579 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-88285755-G-A is Benign according to our data. Variant chr10-88285755-G-A is described in ClinVar as Benign. ClinVar VariationId is 1274833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 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.877-249C>T		intron	N/A	NP_001026879.2	Q5VYX0-1
	RNLS	NM_018363.4		c.877-10723C>T		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.877-249C>T		intron	N/A	ENSP00000332530.4	Q5VYX0-1
	RNLS	ENST00000371947.7	TSL:2	c.877-10723C>T		intron	N/A	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10711 AN: 151976 Hom.: 580 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.00714

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0628

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

GnomAD4 genome AF: 0.0706 AC: 10731 AN: 152094 Hom.: 579 Cov.: 32 AF XY: 0.0694 AC XY: 5159 AN XY: 74352

African (AFR) AF: 0.151 AC: 6270 AN: 41472

American (AMR) AF: 0.0622 AC: 950 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3468

East Asian (EAS) AF: 0.00716 AC: 37 AN: 5168

South Asian (SAS) AF: 0.0502 AC: 242 AN: 4822

European-Finnish (FIN) AF: 0.0325 AC: 344 AN: 10598

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2548 AN: 67976

Other (OTH) AF: 0.0636 AC: 134 AN: 2108

Alfa AF: 0.0529 Hom.: 116

Bravo AF: 0.0779

Asia WGS AF: 0.0550 AC: 192 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.77
PhyloP100		0.14
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: rs74146690; hg19: chr10-90045512;