Variant 10-88274730-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018363.4(RNLS):c.*231G>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 0.00289 in 417,790 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

RNLS
NM_018363.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 10-88274730-C-T is Benign according to our data. Variant chr10-88274730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1320572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00642 (978/152252) while in subpopulation AFR AF= 0.0223 (925/41546). AF 95% confidence interval is 0.0211. There are 7 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
RNLS	NM_018363.4 linkuse as main transcript	c.*231G>A	3_prime_UTR_variant	7/7	NP_060833.1	Q5VYX0-2
RNLS	XM_011539924.4 linkuse as main transcript	c.*28+203G>A	intron_variant		XP_011538226.1	Q5VYX0-2
RNLS	XM_017016380.3 linkuse as main transcript	c.*28+203G>A	intron_variant		XP_016871869.1	Q5VYX0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000371947 linkuse as main transcript	c.*231G>A		3_prime_UTR_variant	7/7	2		ENSP00000361015.3		Q5VYX0-2

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.000862

AC:

229

AN:

265538

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

AN XY:

140858

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000385

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.00642

AC:

978

AN:

152252

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00564

Hom.:

Bravo

AF:

0.00756

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.18

DANN

Benign

0.48

Splicing

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