rs4934391

Variant names:

• chr10-88288392-G-A
• rs4934391
• NM_001031709.3:c.877-2886C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-88288392-G-A
• chr10-88288392-G-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.877-2886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,932 control chromosomes in the GnomAD database, including 24,661 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 0.56 (24661 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 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.877-2886C>T		intron	N/A	NP_001026879.2
	RNLS	NM_018363.4		c.877-13360C>T		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.877-2886C>T		intron	N/A	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.877-13360C>T		intron	N/A	ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84885 AN: 151816 Hom.: 24663 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.559 AC: 84908 AN: 151932 Hom.: 24661 Cov.: 32 AF XY: 0.561 AC XY: 41667 AN XY: 74270

African (AFR) AF: 0.390 AC: 16174 AN: 41438

American (AMR) AF: 0.613 AC: 9347 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.558 AC: 2880 AN: 5164

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4822

European-Finnish (FIN) AF: 0.682 AC: 7197 AN: 10556

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42671 AN: 67936

Other (OTH) AF: 0.565 AC: 1191 AN: 2108

Alfa AF: 0.589 Hom.: 5894

Bravo AF: 0.547

Asia WGS AF: 0.506 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.29
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: rs4934391; hg19: chr10-90048149;