Genetic Variant ENST00000371947.7:c.-451T>C (chr10-88583641-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.248

Variant links:

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 links:

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]

LIPJ links:

ENSG00000289952 (HGNC:):

ENSG00000289952 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
LIPJ	XM_006717635.4 link	c.-598A>G		5_prime_UTR_variant	Exon 1 of 11		XP_006717698.1	Q5W064
LIPJ	NR_172141.1 link	n.735A>G		non_coding_transcript_exon_variant	Exon 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNLS	ENST00000371947.7 link	c.-451T>C		5_prime_UTR_variant	Exon 1 of 7	2		ENSP00000361015.3		Q5VYX0-2
ENSG00000289952	ENST00000702048.1 link	n.677A>G		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44022

AN:

152056

Hom.:

6689

Cov.:

show subpopulations

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.:

AF XY:

0.273

AC XY:

105436

AN XY:

386136

show subpopulations

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.:

AF XY:

0.292

AC XY:

21738

AN XY:

74428

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over