rs4934396

Variant names:

• chr10-88358401-A-G
• rs4934396
• NM_001031709.3:c.700+4151T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031709.3(RNLS):​c.700+4151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 152,266 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (495 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.700+4151T>C		intron	N/A	NP_001026879.2
	RNLS	NM_018363.4		c.700+4151T>C		intron	N/A	NP_060833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.700+4151T>C		intron	N/A	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.700+4151T>C		intron	N/A	ENSP00000361015.3
	RNLS	ENST00000466945.5	TSL:3	n.683+4151T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10197 AN: 152148 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0670 AC: 10201 AN: 152266 Hom.: 495 Cov.: 32 AF XY: 0.0663 AC XY: 4937 AN XY: 74442

African (AFR) AF: 0.0154 AC: 641 AN: 41572

American (AMR) AF: 0.127 AC: 1949 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 324 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.121 AC: 583 AN: 4816

European-Finnish (FIN) AF: 0.0559 AC: 593 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5819 AN: 68016

Other (OTH) AF: 0.0730 AC: 154 AN: 2110

Alfa AF: 0.0785 Hom.: 198

Bravo AF: 0.0705

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4934396; hg19: chr10-90118158;