10-88273836-A-G

Variant names:

• chr10-88273836-A-G
• rs2114406
• XM_011539924.4:c.*28+1097T>C

Variant summary

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

The XM_011539924.4(RNLS):​c.*28+1097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 149,258 control chromosomes in the GnomAD database, including 6,993 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 0.29 (6993 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: RNLS XM_011539924.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371947.7. 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_018363.4		c.*1125T>C		downstream_gene	N/A	NP_060833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000371947.7	TSL:2	c.*1125T>C		downstream_gene	N/A	ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 43776 AN: 149146 Hom.: 6999 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.310

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.293 AC: 43778 AN: 149258 Hom.: 6993 Cov.: 33 AF XY: 0.300 AC XY: 21861 AN XY: 72836

African (AFR) AF: 0.169 AC: 6876 AN: 40652

American (AMR) AF: 0.283 AC: 4243 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1363 AN: 3430

East Asian (EAS) AF: 0.230 AC: 1175 AN: 5098

South Asian (SAS) AF: 0.375 AC: 1733 AN: 4618

European-Finnish (FIN) AF: 0.461 AC: 4780 AN: 10366

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22565 AN: 66876

Other (OTH) AF: 0.310 AC: 634 AN: 2046

Alfa AF: 0.329 Hom.: 15491

Bravo AF: 0.268

Asia WGS AF: 0.284 AC: 986 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs2114406; hg19: chr10-90033593;