10-88284588-A-G

Variant names:

• chr10-88284588-A-G
• rs10749571
• NM_001031709.3:c.*766T>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.*766T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 985,022 control chromosomes in the GnomAD database, including 389,770 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 0.87 (57602 hom., cov: 33)
  • Exomes 𝑓: 0.89 (332168 hom.)
• Consequence: RNLS NM_001031709.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 10 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 = 0.884 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.*766T>C		3_prime_UTR	Exon 7 of 7	NP_001026879.2
	RNLS	NM_018363.4		c.877-9556T>C		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.*766T>C		3_prime_UTR	Exon 7 of 7	ENSP00000332530.4
	RNLS	ENST00000371947.7	TSL:2	c.877-9556T>C		intron	N/A	ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132161 AN: 152056 Hom.: 57551 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.865

GnomAD4 exome AF: 0.893 AC: 743712 AN: 832848 Hom.: 332168 Cov.: 27 AF XY: 0.894 AC XY: 343802 AN XY: 384598

African (AFR) AF: 0.823 AC: 12999 AN: 15786

American (AMR) AF: 0.885 AC: 871 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 4252 AN: 5152

East Asian (EAS) AF: 0.813 AC: 2951 AN: 3628

South Asian (SAS) AF: 0.907 AC: 14928 AN: 16452

European-Finnish (FIN) AF: 0.899 AC: 248 AN: 276

Middle Eastern (MID) AF: 0.883 AC: 1430 AN: 1620

European-Non Finnish (NFE) AF: 0.895 AC: 681996 AN: 761664

Other (OTH) AF: 0.881 AC: 24037 AN: 27286

GnomAD4 genome AF: 0.869 AC: 132273 AN: 152174 Hom.: 57602 Cov.: 33 AF XY: 0.870 AC XY: 64722 AN XY: 74388

African (AFR) AF: 0.834 AC: 34599 AN: 41510

American (AMR) AF: 0.867 AC: 13253 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2844 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4138 AN: 5172

South Asian (SAS) AF: 0.904 AC: 4362 AN: 4824

European-Finnish (FIN) AF: 0.917 AC: 9712 AN: 10592

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60501 AN: 68004

Other (OTH) AF: 0.864 AC: 1826 AN: 2114

Alfa AF: 0.879 Hom.: 101226

Bravo AF: 0.864

Asia WGS AF: 0.852 AC: 2961 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.37
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10749571; hg19: chr10-90044345;