10-88314644-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001031709.3(RNLS):c.701-3C>T variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0109 in 1,612,272 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (127 hom., cov: 32)
  • Exomes 𝑓: 0.011 (775 hom.)
• Consequence: RNLS NM_001031709.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006815
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.48

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-88314644-G-A is Benign according to our data. Variant chr10-88314644-G-A is described in ClinVar as [Benign]. Clinvar id is 1252316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.701-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-55435G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.701-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.701-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
RNLS	ENST00000466945.5	n.684-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2150 AN: 152204 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.00951

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0280 AC: 6993 AN: 249536 Hom.: 369 AF XY: 0.0291 AC XY: 3923 AN XY: 134792

Gnomad AFR exome AF: 0.00321

Gnomad AMR exome AF: 0.0955

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00753

Gnomad SAS exome AF: 0.0998

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0105 AC: 15355 AN: 1459950 Hom.: 775 Cov.: 31 AF XY: 0.0127 AC XY: 9255 AN XY: 726068

Gnomad4 AFR exome AF: 0.00308

Gnomad4 AMR exome AF: 0.0960

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00605

Gnomad4 SAS exome AF: 0.0979

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.000801

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0141 AC: 2154 AN: 152322 Hom.: 127 Cov.: 32 AF XY: 0.0179 AC XY: 1335 AN XY: 74472

Gnomad4 AFR AF: 0.00375

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.00951

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00338 Hom.: 6

Bravo AF: 0.0146

Asia WGS AF: 0.0610 AC: 214 AN: 3478

EpiCase AF: 0.00197

EpiControl AF: 0.00131

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	15
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00068
dbscSNV1_RF	Benign	0.20
SpliceAI score (max)		0.090		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: rs114231964; hg19: chr10-90074401;