10-88285726-A-T

Position:

• chr10-88285726-A-T

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.877-220T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,102 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (558 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0820

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=-0.76).
• BP6: Variant 10-88285726-A-T is Benign according to our data. Variant chr10-88285726-A-T is described in ClinVar as [Benign]. Clinvar id is 1269056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.877-220T>A		intron_variant		ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.877-220T>A		intron_variant		1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.877-10694T>A		intron_variant		2		ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10559 AN: 151984 Hom.: 559 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.00715

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0696 AC: 10579 AN: 152102 Hom.: 558 Cov.: 32 AF XY: 0.0685 AC XY: 5092 AN XY: 74362

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0617

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.00716

Gnomad4 SAS AF: 0.0502

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0561 Hom.: 49

Bravo AF: 0.0767

Asia WGS AF: 0.0540 AC: 189 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.8
DANN	Benign	0.88

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: rs74146689; hg19: chr10-90045483;