10-88314229-G-A

Position:

• chr10-88314229-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+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,176 control chromosomes in the GnomAD database, including 1,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1660 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

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 10-88314229-G-A is Benign according to our data. Variant chr10-88314229-G-A is described in ClinVar as [Benign]. Clinvar id is 1241144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.876+237C>T		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-55850G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.876+237C>T		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.876+237C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21352 AN: 152058 Hom.: 1665 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.140 AC: 21342 AN: 152176 Hom.: 1660 Cov.: 32 AF XY: 0.142 AC XY: 10539 AN XY: 74390

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.148

Alfa AF: 0.146 Hom.: 292

Bravo AF: 0.137

Asia WGS AF: 0.193 AC: 670 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 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.61

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: rs2241515; hg19: chr10-90073986;