chr10-88274731-A-G

Variant names:

• chr10-88274731-A-G
• rs10749568
• NM_018363.4:c.*230T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018363.4(RNLS):​c.*230T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 407,610 control chromosomes in the GnomAD database, including 150,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53484 hom., cov: 31)
  • Exomes 𝑓: 0.87 (96844 hom.)
• Consequence: RNLS NM_018363.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.371
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 10-88274731-A-G is Benign according to our data. Variant chr10-88274731-A-G is described in ClinVar as Benign. ClinVar VariationId is 1232021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018363.4. 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_018363.4		c.*230T>C		3_prime_UTR	Exon 7 of 7	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000371947.7	TSL:2	c.*230T>C		3_prime_UTR	Exon 7 of 7	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127052 AN: 151944 Hom.: 53450 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.840

GnomAD4 exome AF: 0.870 AC: 222214 AN: 255548 Hom.: 96844 Cov.: 2 AF XY: 0.870 AC XY: 117968 AN XY: 135620

African (AFR) AF: 0.741 AC: 5903 AN: 7964

American (AMR) AF: 0.845 AC: 11052 AN: 13086

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 6504 AN: 7768

East Asian (EAS) AF: 0.816 AC: 14437 AN: 17694

South Asian (SAS) AF: 0.860 AC: 25757 AN: 29946

European-Finnish (FIN) AF: 0.895 AC: 12452 AN: 13916

Middle Eastern (MID) AF: 0.836 AC: 918 AN: 1098

European-Non Finnish (NFE) AF: 0.887 AC: 132686 AN: 149598

Other (OTH) AF: 0.864 AC: 12505 AN: 14478

GnomAD4 genome AF: 0.836 AC: 127148 AN: 152062 Hom.: 53484 Cov.: 31 AF XY: 0.835 AC XY: 62074 AN XY: 74300

African (AFR) AF: 0.742 AC: 30747 AN: 41426

American (AMR) AF: 0.839 AC: 12825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2876 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4123 AN: 5176

South Asian (SAS) AF: 0.862 AC: 4138 AN: 4800

European-Finnish (FIN) AF: 0.891 AC: 9425 AN: 10580

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60235 AN: 68004

Other (OTH) AF: 0.841 AC: 1774 AN: 2110

Alfa AF: 0.864 Hom.: 138677

Bravo AF: 0.828

Asia WGS AF: 0.826 AC: 2870 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10749568; hg19: chr10-90034488;