Genetic Variant RNLS:c.701-1445T>C (chr10-88316086-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031709.3(RNLS):c.701-1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,996 control chromosomes in the GnomAD database, including 15,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.45 ( 15888 hom., cov: 32)

Consequence

RNLS
NM_001031709.3 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.0540

Publications

36 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 Gene-Disease associations (from GenCC):

cataract
Inheritance: AR Classification: LIMITED Submitted by: G2P

RNLS links:

LOC101929727 (HGNC:):

LOC101929727 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 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.701-1445T>C		intron	N/A	NP_001026879.2
	RNLS	NM_018363.4		c.701-1445T>C		intron	N/A	NP_060833.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNLS	ENST00000331772.9	TSL:1 MANE Select	c.701-1445T>C	intron	N/A	ENSP00000332530.4
RNLS	ENST00000371947.7	TSL:2	c.701-1445T>C	intron	N/A	ENSP00000361015.3
RNLS	ENST00000466945.5	TSL:3	n.684-1445T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68212

AN:

151878

Hom.:

15881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.444

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

GnomAD4 genome

AF:

0.449

AC:

68248

AN:

151996

Hom.:

15888

Cov.:

AF XY:

0.453

AC XY:

33629

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.318

AC:

13182

AN:

41448

American (AMR)

AF:

0.437

AC:

6666

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1783

AN:

3472

East Asian (EAS)

AF:

0.505

AC:

2615

AN:

5174

South Asian (SAS)

AF:

0.585

AC:

2824

AN:

4826

European-Finnish (FIN)

AF:

0.527

AC:

5551

AN:

10534

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34304

AN:

67956

Other (OTH)

AF:

0.445

AC:

941

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1871

3741

5612

7482

9353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.479

Hom.:

49154

Bravo

AF:

0.429

Asia WGS

AF:

0.492

AC:

1715

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Family history

Other:1

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

Significance:association

Review Status:no assertion criteria provided

Collection Method:case-control

The C-G haplotype represented by the SNPs rs2296545 and rs10887800 in the RNLS gene may have a role in the pathophysiology of CKD in patients with a family history.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.0

(source)

DANN

Benign

0.86

PhyloP100

0.054

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over