10-88314383-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.876+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,371,064 control chromosomes in the GnomAD database, including 81,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7394 hom., cov: 32)
  • Exomes 𝑓: 0.34 (74316 hom.)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.254

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=-0.9).
• BP6: Variant 10-88314383-G-A is Benign according to our data. Variant chr10-88314383-G-A is described in ClinVar as [Benign]. Clinvar id is 1273084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.876+83C>T		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-55696G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.876+83C>T		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.876+83C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45958 AN: 151736 Hom.: 7393 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.345 AC: 420360 AN: 1219210 Hom.: 74316 AF XY: 0.348 AC XY: 211962 AN XY: 609350

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.303 AC: 45995 AN: 151854 Hom.: 7394 Cov.: 32 AF XY: 0.306 AC XY: 22723 AN XY: 74228

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.295

Alfa AF: 0.330 Hom.: 1047

Bravo AF: 0.286

Asia WGS AF: 0.315 AC: 1098 AN: 3478

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 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.78
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11202710; hg19: chr10-90074140; COSMIC: COSV59302515; COSMIC: COSV59302515;