10-88316086-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031709.3(RNLS):c.701-1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,996 control chromosomes in the GnomAD database, including 15,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.45 (15888 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0540

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.701-1445T>C		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-53993A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.701-1445T>C		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.701-1445T>C		intron_variant		2
RNLS	ENST00000466945.5	n.684-1445T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68212 AN: 151878 Hom.: 15881 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.449 AC: 68248 AN: 151996 Hom.: 15888 Cov.: 32 AF XY: 0.453 AC XY: 33629 AN XY: 74292

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.445

Alfa AF: 0.493 Hom.: 30933

Bravo AF: 0.429

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Family history Other:1

association, no assertion criteria provided

case-control

Bioinformatics & Molecular Biology Unit, Faculty of Science, Al-Azhar University

-

The C-G haplotype represented by the SNPs rs2296545 and rs10887800 in the RNLS gene may have a role in the pathophysiology of CKD in patients with a family history. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	7.0
Dann	Benign	0.86

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: rs10887800; hg19: chr10-90075843;