rs11816967

chr10-88428851-A-Gchr10-88428851-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031709.3(RNLS):c.527-66126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,950 control chromosomes in the GnomAD database, including 2,738 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 0.17 (2738 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNLS	NM_001031709.3	c.527-66126T>C		intron_variant		ENST00000331772.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000331772.9	c.527-66126T>C		intron_variant		1	NM_001031709.3	P1
RNLS	ENST00000371947.7	c.527-66126T>C		intron_variant		2
RNLS	ENST00000466945.5	n.510-66126T>C		intron_variant, non_coding_transcript_variant		3
RNLS	ENST00000481793.1	n.418-66126T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25108 AN: 151832 Hom.: 2738 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.165 AC: 25105 AN: 151950 Hom.: 2738 Cov.: 32 AF XY: 0.160 AC XY: 11915 AN XY: 74272

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0663

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.162

Alfa AF: 0.192 Hom.: 393

Bravo AF: 0.157

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.5
Dann	Benign	0.42

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: rs11816967; hg19: chr10-90188608;