10-88449581-C-G

Variant names:

• chr10-88449581-C-G
• rs11202748
• NM_001031709.3:c.527-86856G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001031709.3(RNLS):​c.527-86856G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00851 in 152,120 control chromosomes in the GnomAD database, including 22 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 0.0085 (22 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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=-0.67).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00851 (1294/152120) while in subpopulation EAS AF= 0.0328 (170/5178). AF 95% confidence interval is 0.0288. There are 22 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNLS	NM_001031709.3	c.527-86856G>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.527-86856G>C		intron_variant	Intron 4 of 6	1	NM_001031709.3	ENSP00000332530.4
RNLS	ENST00000371947.7	c.527-86856G>C		intron_variant	Intron 4 of 6	2		ENSP00000361015.3
RNLS	ENST00000466945.5	n.510-86856G>C		intron_variant	Intron 3 of 4	3
RNLS	ENST00000481793.1	n.418-86856G>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00853 AC: 1296 AN: 152002 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.00851 AC: 1294 AN: 152120 Hom.: 22 Cov.: 32 AF XY: 0.0112 AC XY: 835 AN XY: 74384

Gnomad4 AFR AF: 0.000603

Gnomad4 AMR AF: 0.00609

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.00421

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00489 Hom.: 164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.73

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: rs11202748; hg19: chr10-90209338;