rs11816967

Variant names:

• chr10-88428851-A-G
• rs11816967
• NM_001031709.3:c.527-66126T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-88428851-A-G
• chr10-88428851-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.527-66126T>C		intron_variant	Intron 4 of 6	ENST00000331772.9	NP_001026879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000331772.9	c.527-66126T>C		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-66126T>C		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-66126T>C		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-66126T>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.0461 AC: 1915 AN: 41518

American (AMR) AF: 0.151 AC: 2292 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3458

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.0663 AC: 320 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2249 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17266 AN: 67836

Other (OTH) AF: 0.162 AC: 343 AN: 2114

Alfa AF: 0.187 Hom.: 394

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
PhyloP100		0.47
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: rs11816967; hg19: chr10-90188608;