rs4934396

Positions:

• chr10-88358401-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.700+4151T>C		intron_variant		ENST00000331772.9	NP_001026879.2
LOC101929727	XR_001747537.3	n.443-11678A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.700+4151T>C		intron_variant		1	NM_001031709.3	ENSP00000332530	P1
RNLS	ENST00000371947.7	c.700+4151T>C		intron_variant		2		ENSP00000361015
RNLS	ENST00000466945.5	n.683+4151T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0804 Hom.: 103

Bravo AF: 0.0705

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.4
DANN	Benign	0.68

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: rs4934396; hg19: chr10-90118158;