10-88285755-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001031709.3(RNLS):c.877-249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 152,094 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (579 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143

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]

LOC101929727 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-88285755-G-A is Benign according to our data. Variant chr10-88285755-G-A is described in ClinVar as [Benign]. Clinvar id is 1274833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.877-249C>T		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-84324G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.877-249C>T		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.877-10723C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10711 AN: 151976 Hom.: 580 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.00714

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0628

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0706 AC: 10731 AN: 152094 Hom.: 579 Cov.: 32 AF XY: 0.0694 AC XY: 5159 AN XY: 74352

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0622

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.00716

Gnomad4 SAS AF: 0.0502

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0636

Alfa AF: 0.0517 Hom.: 65

Bravo AF: 0.0779

Asia WGS AF: 0.0550 AC: 192 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.9
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs74146690; hg19: chr10-90045512;