Genetic Variant NM_018363.4:c.877-110G>A (chr10-88275142-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.877-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 816,896 control chromosomes in the GnomAD database, including 24,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4274 hom., cov: 32)

Exomes 𝑓: 0.25 ( 20522 hom. )

Consequence

RNLS
NM_018363.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0830

Publications

5 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=-0.75).

BP6

Variant 10-88275142-C-T is Benign according to our data. Variant chr10-88275142-C-T is described in ClinVar as Benign. ClinVar VariationId is 1257899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 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.877-110G>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.877-110G>A		intron	N/A	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35782

AN:

151826

Hom.:

4265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.234

GnomAD4 exome

AF:

0.245

AC:

163147

AN:

664954

Hom.:

20522

AF XY:

0.247

AC XY:

86189

AN XY:

348424

show subpopulations

African (AFR)

AF:

0.220

AC:

3850

AN:

17494

American (AMR)

AF:

0.172

AC:

5409

AN:

31424

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

4147

AN:

18402

East Asian (EAS)

AF:

0.216

AC:

6907

AN:

31972

South Asian (SAS)

AF:

0.277

AC:

15946

AN:

57656

European-Finnish (FIN)

AF:

0.211

AC:

9237

AN:

43752

Middle Eastern (MID)

AF:

0.173

AC:

705

AN:

4070

European-Non Finnish (NFE)

AF:

0.255

AC:

109010

AN:

427208

Other (OTH)

AF:

0.241

AC:

7936

AN:

32976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5673

11347

17020

22694

28367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2076

4152

6228

8304

10380

<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:

0.236

AC:

35833

AN:

151942

Hom.:

4274

Cov.:

AF XY:

0.234

AC XY:

17357

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.224

AC:

9280

AN:

41464

American (AMR)

AF:

0.201

AC:

3064

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

773

AN:

3464

East Asian (EAS)

AF:

0.203

AC:

1046

AN:

5148

South Asian (SAS)

AF:

0.270

AC:

1302

AN:

4820

European-Finnish (FIN)

AF:

0.210

AC:

2214

AN:

10548

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17391

AN:

67938

Other (OTH)

AF:

0.238

AC:

502

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1384

2769

4153

5538

6922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.243

Hom.:

709

Bravo

AF:

0.234

Asia WGS

AF:

0.278

AC:

966

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

-0.75

CADD

Benign

9.0

(source)

DANN

Benign

0.89

PhyloP100

-0.083

Mutation Taster

=100/0

polymorphism (auto)

(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