10-88583080-C-G

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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:2 O:1
• Conservation: PhyloP100: -0.517

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.111G>C	p.Glu37Asp	missense_variant	1/7	ENST00000331772.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.111G>C	p.Glu37Asp	missense_variant	1/7	1	NM_001031709.3	P1
	ENST00000702048.1	n.116C>G		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.457 AC: 112796 AN: 246570 Hom.: 26303 AF XY: 0.456 AC XY: 60755 AN XY: 133376

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 SAS exome AF: 0.463

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

Gnomad4 AFR exome AF: 0.530

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.447

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

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.465

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:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 07, 2018	This variant is associated with the following publications: (PMID: 20975995, 23116393, 27434211, 22812913, 24923329, 26309615, 29065134, 17216203) -

Stage 5 chronic kidney disease Other:1

association, no assertion criteria provided

case-control

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

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Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.000026	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.42	N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.19	B;B;.
Vest4		0.037
MutPred		0.12		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MPC		0.11
ClinPred		0.0096	T
GERP RS		-0.83
Varity_R		0.13
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296545; hg19: chr10-90342837; COSMIC: COSV59290594; COSMIC: COSV59290594;