NM_001031709.3:c.111G>C

Variant names:

• chr10-88583080-C-G
• rs2296545
• NM_001031709.3:c.111G>C

Variant summary

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

The NM_001031709.3(RNLS):​c.111G>C​(p.Glu37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,608,540 control chromosomes in the GnomAD database, including 159,205 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17133 hom., cov: 33)
  • Exomes 𝑓: 0.44 (142072 hom.)
• Consequence: RNLS NM_001031709.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.517
• Publications: 90 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]

ENSG00000289952 (HGNC:):

LIPJ (HGNC:21773): (lipase family member J) Predicted to enable hydrolase activity, acting on ester bonds. Predicted to be involved in lipid catabolic process. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.648983E-5).
• BP6: Variant 10-88583080-C-G is Benign according to our data. Variant chr10-88583080-C-G is described in ClinVar as Benign. ClinVar VariationId is 1250700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.111G>C	p.Glu37Asp	missense	Exon 1 of 7	NP_001026879.2
	RNLS	NM_018363.4		c.111G>C	p.Glu37Asp	missense	Exon 1 of 7	NP_060833.1
	LIPJ	NR_172141.1		n.174C>G		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.111G>C	p.Glu37Asp	missense	Exon 1 of 7	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.111G>C	p.Glu37Asp	missense	Exon 1 of 7	ENSP00000361015.3
	RNLS	ENST00000466945.5	TSL:3	n.253G>C		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71749 AN: 152042 Hom.: 17124 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.457 AC: 112796 AN: 246570 AF XY: 0.456

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.465

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.538

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.439 AC: 640025 AN: 1456380 Hom.: 142072 Cov.: 43 AF XY: 0.440 AC XY: 318249 AN XY: 723934

African (AFR) AF: 0.530 AC: 17585 AN: 33186

American (AMR) AF: 0.460 AC: 20260 AN: 44090

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12421 AN: 25996

East Asian (EAS) AF: 0.417 AC: 16443 AN: 39436

South Asian (SAS) AF: 0.463 AC: 39715 AN: 85720

European-Finnish (FIN) AF: 0.530 AC: 28269 AN: 53294

Middle Eastern (MID) AF: 0.493 AC: 2836 AN: 5748

European-Non Finnish (NFE) AF: 0.429 AC: 475615 AN: 1108812

Other (OTH) AF: 0.447 AC: 26881 AN: 60098

GnomAD4 genome AF: 0.472 AC: 71791 AN: 152160 Hom.: 17133 Cov.: 33 AF XY: 0.475 AC XY: 35346 AN XY: 74380

African (AFR) AF: 0.523 AC: 21697 AN: 41512

American (AMR) AF: 0.439 AC: 6719 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1668 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5162

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5807 AN: 10588

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29711 AN: 67986

Other (OTH) AF: 0.465 AC: 983 AN: 2112

Alfa AF: 0.419 Hom.: 9970

Bravo AF: 0.467

TwinsUK AF: 0.417 AC: 1547

ALSPAC AF: 0.428 AC: 1651

ESP6500AA AF: 0.537 AC: 2367

ESP6500EA AF: 0.434 AC: 3735

ExAC AF: 0.460 AC: 55835

Asia WGS AF: 0.460 AC: 1602 AN: 3478

EpiCase AF: 0.428

EpiControl AF: 0.430

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20975995, 23116393, 27434211, 22812913, 24923329, 26309615, 29065134, 17216203)

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Stage 5 chronic kidney disease Other:1

Bioinformatics & Molecular Biology Unit, Faculty of Science, Al-Azhar University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.000026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.42	N
PhyloP100		-0.52
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.073
Sift	Benign	0.49	T
Sift4G	Benign	0.19	T
Polyphen		0.19	B
Vest4		0.037
MutPred		0.12		Loss of helix (P = 0.0626)
MPC		0.11
ClinPred		0.0096	T
GERP RS		-0.83
PromoterAI		0.12	Neutral
Varity_R		0.13
gMVP		0.33
Mutation Taster		=91/9	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: rs2296545; hg19: chr10-90342837; COSMIC: COSV59290594; COSMIC: COSV59290594;