10-88314248-A-G

Position:

• chr10-88314248-A-G

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+218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,140 control chromosomes in the GnomAD database, including 4,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4547 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-88314248-A-G is Benign according to our data. Variant chr10-88314248-A-G is described in ClinVar as [Benign]. Clinvar id is 1261364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.876+218T>C		intron_variant		ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.876+218T>C		intron_variant		1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.876+218T>C		intron_variant		2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34704 AN: 152022 Hom.: 4544 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.228 AC: 34721 AN: 152140 Hom.: 4547 Cov.: 32 AF XY: 0.233 AC XY: 17294 AN XY: 74362

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.221

Alfa AF: 0.258 Hom.: 1015

Bravo AF: 0.211

Asia WGS AF: 0.246 AC: 860 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.40

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: rs11202709; hg19: chr10-90074005;