Genetic Variant RNLS:c.-451T>C (chr10-88583641-A-G) – 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 ENST00000371947.7(RNLS):c.-451T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 988,076 control chromosomes in the GnomAD database, including 38,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6699 hom., cov: 32)

Exomes 𝑓: 0.27 ( 31577 hom. )

Consequence

RNLS
ENST00000371947.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.248

Publications

45 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:

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:

ENSG00000289952 (HGNC:):

ENSG00000289952 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=-0.86).

BP6

Variant 10-88583641-A-G is Benign according to our data. Variant chr10-88583641-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371947.7. 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
	LIPJ	NR_172141.1		n.735A>G		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000371947.7	TSL:2	c.-451T>C		5_prime_UTR	Exon 1 of 7	ENSP00000361015.3	Q5VYX0-2
	ENSG00000289952	ENST00000702048.2		n.735A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44022

AN:

152056

Hom.:

6689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.274

AC:

228742

AN:

835902

Hom.:

31577

Cov.:

AF XY:

0.273

AC XY:

105436

AN XY:

386136

show subpopulations

African (AFR)

AF:

0.266

AC:

4224

AN:

15862

American (AMR)

AF:

0.430

AC:

470

AN:

1094

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1762

AN:

5222

East Asian (EAS)

AF:

0.537

AC:

1988

AN:

3704

South Asian (SAS)

AF:

0.278

AC:

4661

AN:

16770

European-Finnish (FIN)

AF:

0.250

AC:

AN:

384

Middle Eastern (MID)

AF:

0.256

AC:

416

AN:

1626

European-Non Finnish (NFE)

AF:

0.271

AC:

207205

AN:

763790

Other (OTH)

AF:

0.289

AC:

7920

AN:

27450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

9013

18026

27038

36051

45064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9580

19160

28740

38320

47900

<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:

0.290

AC:

44056

AN:

152174

Hom.:

6699

Cov.:

AF XY:

0.292

AC XY:

21738

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.268

AC:

11148

AN:

41524

American (AMR)

AF:

0.362

AC:

5534

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1199

AN:

3468

East Asian (EAS)

AF:

0.535

AC:

2767

AN:

5170

South Asian (SAS)

AF:

0.290

AC:

1400

AN:

4828

European-Finnish (FIN)

AF:

0.242

AC:

2570

AN:

10598

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18620

AN:

67986

Other (OTH)

AF:

0.305

AC:

644

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1573

3145

4718

6290

7863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.283

Hom.:

7659

Bravo

AF:

0.297

Asia WGS

AF:

0.425

AC:

1473

AN:

3478

ClinVar

ClinVar submissions

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

-0.86

CADD

Benign

2.3

(source)

DANN

Benign

0.40

PhyloP100

0.25

PromoterAI

-0.036

Neutral

(source)

Mutation Taster

=300/0

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