chr10-88263276-T-C

Variant names:

• chr10-88263276-T-C
• rs10509540
• XM_017016380.3:c.*2759A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017016380.3(RNLS):​c.*2759A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,988 control chromosomes in the GnomAD database, including 4,893 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 0.25 (4893 hom., cov: 31)
• Consequence: RNLS XM_017016380.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 75 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	XM_017016380.3	c.*2759A>G		3_prime_UTR_variant	Exon 8 of 8		XP_016871869.1
RNLS	XM_011539924.4	c.*28+11657A>G		intron_variant	Intron 7 of 7		XP_011538226.1
RNLS	XM_017016382.3	c.*28+11657A>G		intron_variant	Intron 5 of 5		XP_016871871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38461 AN: 151866 Hom.: 4889 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.253 AC: 38485 AN: 151988 Hom.: 4893 Cov.: 31 AF XY: 0.255 AC XY: 18933 AN XY: 74306

African (AFR) AF: 0.225 AC: 9315 AN: 41418

American (AMR) AF: 0.238 AC: 3635 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5178

South Asian (SAS) AF: 0.340 AC: 1635 AN: 4810

European-Finnish (FIN) AF: 0.246 AC: 2598 AN: 10574

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18477 AN: 67960

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.264 Hom.: 23364

Bravo AF: 0.252

Asia WGS AF: 0.307 AC: 1070 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10509540; hg19: chr10-90023033;