rs4934391

chr10-88288392-G-Achr10-88288392-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.877-2886C>T		intron_variant		ENST00000331772.9
LOC101929727	XR_001747537.3	n.443-81687G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.877-2886C>T		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.877-13360C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.565

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.5
Dann	Benign	0.81

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: rs4934391; hg19: chr10-90048149;