dbSNP rs78147033: RNLS:c.*270G>A (chr10-88274691-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.*270G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 357,106 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 131 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 14 hom. )

Consequence

RNLS
NM_018363.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.631

Publications

0 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=-0.88).

BP6

Variant 10-88274691-C-T is Benign according to our data. Variant chr10-88274691-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 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.*270G>A		3_prime_UTR	Exon 7 of 7	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000371947.7	TSL:2	c.*270G>A		3_prime_UTR	Exon 7 of 7	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3248

AN:

152156

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0134

GnomAD4 exome

AF:

0.00290

AC:

594

AN:

204832

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

277

AN XY:

108452

show subpopulations

African (AFR)

AF:

0.0709

AC:

481

AN:

6788

American (AMR)

AF:

0.00341

AC:

AN:

11160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6204

East Asian (EAS)

AF:

0.00

AC:

AN:

13394

South Asian (SAS)

AF:

0.000194

AC:

AN:

25784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9872

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

846

European-Non Finnish (NFE)

AF:

0.000126

AC:

AN:

119124

Other (OTH)

AF:

0.00446

AC:

AN:

11660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0214

AC:

3259

AN:

152274

Hom.:

131

Cov.:

AF XY:

0.0209

AC XY:

1554

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0748

AC:

3105

AN:

41534

American (AMR)

AF:

0.00700

AC:

107

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68026

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

152

304

456

608

760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0113

Hom.:

Bravo

AF:

0.0236

Asia WGS

AF:

0.00375

AC:

AN:

3478

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

-0.88

CADD

Benign

3.8

(source)

DANN

Benign

0.80

PhyloP100

-0.63

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