Genetic Variant NM_018363.4:c.877-94G>A (chr10-88275126-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_018363.4(RNLS):c.877-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 973,534 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 181 hom., cov: 32)

Exomes 𝑓: 0.029 ( 487 hom. )

Consequence

RNLS
NM_018363.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.642

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 10-88275126-C-T is Benign according to our data. Variant chr10-88275126-C-T is described in ClinVar as Benign. ClinVar VariationId is 1264620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 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.877-94G>A		intron	N/A	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000371947.7	TSL:2	c.877-94G>A		intron	N/A	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6428

AN:

152044

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0778

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00623

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0398

GnomAD4 exome

AF:

0.0295

AC:

24194

AN:

821372

Hom.:

487

AF XY:

0.0285

AC XY:

12238

AN XY:

429392

show subpopulations

African (AFR)

AF:

0.0826

AC:

1711

AN:

20704

American (AMR)

AF:

0.0221

AC:

827

AN:

37430

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

933

AN:

21178

East Asian (EAS)

AF:

0.000582

AC:

AN:

34390

South Asian (SAS)

AF:

0.00764

AC:

526

AN:

68852

European-Finnish (FIN)

AF:

0.00795

AC:

388

AN:

48830

Middle Eastern (MID)

AF:

0.0361

AC:

162

AN:

4486

European-Non Finnish (NFE)

AF:

0.0334

AC:

18266

AN:

546550

Other (OTH)

AF:

0.0349

AC:

1361

AN:

38952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1089

2177

3266

4354

5443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.0425

AC:

6460

AN:

152162

Hom.:

181

Cov.:

AF XY:

0.0392

AC XY:

2919

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0782

AC:

3247

AN:

41512

American (AMR)

AF:

0.0348

AC:

531

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5170

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00623

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0337

AC:

2290

AN:

67998

Other (OTH)

AF:

0.0427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

315

630

944

1259

1574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0411

Hom.:

Bravo

AF:

0.0473

Asia WGS

AF:

0.0320

AC:

111

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over