10-88314388-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+78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,427,590 control chromosomes in the GnomAD database, including 82,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6874 hom., cov: 32)
  • Exomes 𝑓: 0.34 (75442 hom.)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0320

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 10-88314388-A-G is Benign according to our data. Variant chr10-88314388-A-G is described in ClinVar as [Benign]. Clinvar id is 1273010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.876+78T>C		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-55691A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.876+78T>C		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.876+78T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43300 AN: 151778 Hom.: 6874 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.339 AC: 432948 AN: 1275694 Hom.: 75442 AF XY: 0.341 AC XY: 217011 AN XY: 635650

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.285 AC: 43330 AN: 151896 Hom.: 6874 Cov.: 32 AF XY: 0.288 AC XY: 21364 AN XY: 74232

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.280

Alfa AF: 0.318 Hom.: 1004

Bravo AF: 0.267

Asia WGS AF: 0.288 AC: 1006 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	1.4
Dann	Benign	0.60

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: rs11202711; hg19: chr10-90074145; COSMIC: COSV59302524; COSMIC: COSV59302524;