rs114231964

Variant names:

• chr10-88314644-G-A
• rs114231964
• NM_001031709.3:c.701-3C>T

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.0006815
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.48
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

LOC101929727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.701-3C>T		splice_region intron	N/A	NP_001026879.2	Q5VYX0-1
	RNLS	NM_018363.4		c.701-3C>T		splice_region intron	N/A	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.701-3C>T		splice_region intron	N/A	ENSP00000332530.4	Q5VYX0-1
	RNLS	ENST00000371947.7	TSL:2	c.701-3C>T		splice_region intron	N/A	ENSP00000361015.3	Q5VYX0-2
	RNLS	ENST00000466945.5	TSL:3	n.684-3C>T		splice_region intron	N/A

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

GnomAD2 exomes AF: 0.0280 AC: 6993 AN: 249536 AF XY: 0.0291

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 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

African (AFR) AF: 0.00308 AC: 103 AN: 33420

American (AMR) AF: 0.0960 AC: 4278 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00605 AC: 240 AN: 39642

South Asian (SAS) AF: 0.0979 AC: 8407 AN: 85882

European-Finnish (FIN) AF: 0.0115 AC: 611 AN: 53354

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5756

European-Non Finnish (NFE) AF: 0.000801 AC: 890 AN: 1110952

Other (OTH) AF: 0.0124 AC: 746 AN: 60342

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

African (AFR) AF: 0.00375 AC: 156 AN: 41570

American (AMR) AF: 0.0802 AC: 1227 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5188

South Asian (SAS) AF: 0.109 AC: 528 AN: 4828

European-Finnish (FIN) AF: 0.00951 AC: 101 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68034

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs114231964; hg19: chr10-90074401;