Variant 10-88314644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001031709.3(RNLS):c.701-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0109 in 1,612,272 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 127 hom., cov: 32)

Exomes 𝑓: 0.011 ( 775 hom. )

Consequence

RNLS
NM_001031709.3 splice_region, intron

Scores

Splicing: ADA: 0.0006815

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.48

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:

RNLS (HGNC:):

RNLS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 10-88314644-G-A is Benign according to our data. Variant chr10-88314644-G-A is described in ClinVar as [Benign]. Clinvar id is 1252316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_001031709.3 linkuse as main transcript	c.701-3C>T		splice_region_variant, intron_variant		ENST00000331772.9	NP_001026879.2	Q5VYX0-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RNLS	ENST00000331772.9 linkuse as main transcript	c.701-3C>T	splice_region_variant, intron_variant	1	NM_001031709.3	ENSP00000332530.4	Q5VYX0-1
RNLS	ENST00000371947.7 linkuse as main transcript	c.701-3C>T	splice_region_variant, intron_variant	2		ENSP00000361015.3	Q5VYX0-2
RNLS	ENST00000466945.5 linkuse as main transcript	n.684-3C>T	splice_region_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2150

AN:

152204

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0802

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00846

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.00951

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0280

AC:

6993

AN:

249536

Hom.:

369

AF XY:

0.0291

AC XY:

3923

AN XY:

134792

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.0955

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00753

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0105

AC:

15355

AN:

1459950

Hom.:

775

Cov.:

AF XY:

0.0127

AC XY:

9255

AN XY:

726068

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.0960

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00605

Gnomad4 SAS exome

AF:

0.0979

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.000801

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.0141

AC:

2154

AN:

152322

Hom.:

127

Cov.:

AF XY:

0.0179

AC XY:

1335

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00375

Gnomad4 AMR

AF:

0.0802

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00848

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.00951

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.0610

AC:

214

AN:

3478

EpiCase

AF:

0.00197

EpiControl

AF:

0.00131

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00068

dbscSNV1_RF

Benign

0.20

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over