10-88583641-A-G

Position:

• chr10-88583641-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371947.7(RNLS):​c.-451T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 988,076 control chromosomes in the GnomAD database, including 38,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6699 hom., cov: 32)
  • Exomes 𝑓: 0.27 (31577 hom.)
• Consequence: RNLS ENST00000371947.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.248

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]

LIPJ (HGNC:21773): (lipase family member J) Predicted to enable hydrolase activity, acting on ester bonds. Predicted to be involved in lipid catabolic process. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289952 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-88583641-A-G is Benign according to our data. Variant chr10-88583641-A-G is described in ClinVar as [Benign]. Clinvar id is 1239848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPJ	XM_006717635.4	c.-598A>G		5_prime_UTR_variant	1/11		XP_006717698.1
LIPJ	NR_172141.1	n.735A>G		non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000371947.7	c.-451T>C		5_prime_UTR_variant	1/7	2		ENSP00000361015.3
ENSG00000289952	ENST00000702048.1	n.677A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44022 AN: 152056 Hom.: 6689 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.274 AC: 228742 AN: 835902 Hom.: 31577 Cov.: 32 AF XY: 0.273 AC XY: 105436 AN XY: 386136

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.290 AC: 44056 AN: 152174 Hom.: 6699 Cov.: 32 AF XY: 0.292 AC XY: 21738 AN XY: 74428

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.305

Alfa AF: 0.282 Hom.: 5851

Bravo AF: 0.297

Asia WGS AF: 0.425 AC: 1473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	This variant is associated with the following publications: (PMID: 17216203) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2576178; hg19: chr10-90343398;