10-88583080-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.517

Publications

90 publications found

Variant links:

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 links:

ENSG00000289952 (HGNC:):

ENSG00000289952 links:

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]

LIPJ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3 link	c.111G>C	p.Glu37Asp	missense_variant	Exon 1 of 7	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9 link	c.111G>C	p.Glu37Asp	missense_variant	Exon 1 of 7	1	NM_001031709.3	ENSP00000332530.4

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71749

AN:

152042

Hom.:

17124

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.440

AC XY:

318249

AN XY:

723934

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

17639

35278

52916

70555

88194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14628

29256

43884

58512

73140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.472

AC:

71791

AN:

152160

Hom.:

17133

Cov.:

AF XY:

0.475

AC XY:

35346

AN XY:

74380

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2033

4067

6100

8134

10167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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) -

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.000026

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.42

N;N;.

PhyloP100

-0.52

PrimateAI

Benign

0.39

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

GERP RS

-0.83

PromoterAI

0.12

Neutral

(source)

Varity_R

0.13

gMVP

0.33

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over