10-88274788-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The XR_001747537.3(LOC101929727):n.443-95291A>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 492,652 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (123 hom., cov: 32)
  • Exomes 𝑓: 0.028 (203 hom.)
• Consequence: LOC101929727 XR_001747537.3 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.278

Genes affected

LOC101929727 (HGNC:):

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-88274788-A-T is Benign according to our data. Variant chr10-88274788-A-T is described in ClinVar as [Benign]. Clinvar id is 1274518.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101929727	XR_001747537.3	n.443-95291A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNLS	ENST00000371947.7	c.*173T>A		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5412 AN: 152144 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00706

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0276 AC: 9401 AN: 340390 Hom.: 203 Cov.: 3 AF XY: 0.0267 AC XY: 4805 AN XY: 179920

Gnomad4 AFR exome AF: 0.0523

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.000266

Gnomad4 SAS exome AF: 0.00682

Gnomad4 FIN exome AF: 0.00754

Gnomad4 NFE exome AF: 0.0344

Gnomad4 OTH exome AF: 0.0320

GnomAD4 genome AF: 0.0357 AC: 5429 AN: 152262 Hom.: 123 Cov.: 32 AF XY: 0.0328 AC XY: 2439 AN XY: 74450

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.00717 Hom.: 4

Bravo AF: 0.0392

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72818070; hg19: chr10-90034545;