Variant chr13-76992023-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000636183(CLN5):c.-76A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,606,282 control chromosomes in the GnomAD database, including 3,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 785 hom., cov: 33)

Exomes 𝑓: 0.045 ( 2283 hom. )

Consequence

CLN5
ENST00000636183 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

CLN5 (HGNC:2076): (CLN5 intracellular trafficking protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function.[provided by RefSeq, Oct 2008]

CLN5 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=-0.75).

BP6

Variant 13-76992023-A-G is Benign according to our data. Variant chr13-76992023-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 95398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-76992023-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CLN5	ENST00000636183 link	c.-76A>G	5_prime_UTR_variant	Exon 1 of 4	1	ENSP00000490181.2	O75503
CLN5	ENST00000636780.2 link	c.-76A>G	upstream_gene_variant		5	ENSP00000489809.2	A0A1B0GTR6
CLN5	ENST00000485938.4 link	c.-76A>G	upstream_gene_variant		2	ENSP00000482959.3	A0A087WZY0

Frequencies

GnomAD3 genomes

AF:

0.0820

AC:

12477

AN:

152126

Hom.:

788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0717

AC:

15940

AN:

222188

Hom.:

850

AF XY:

0.0638

AC XY:

7878

AN XY:

123470

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.0410

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.0534

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0450

AC:

65399

AN:

1454040

Hom.:

2283

Cov.:

AF XY:

0.0441

AC XY:

31855

AN XY:

723108

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0412

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.0524

Gnomad4 FIN exome

AF:

0.0356

Gnomad4 NFE exome

AF:

0.0336

Gnomad4 OTH exome

AF:

0.0501

GnomAD4 genome

AF:

0.0821

AC:

12499

AN:

152242

Hom.:

785

Cov.:

AF XY:

0.0827

AC XY:

6156

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.0526

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.0337

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0325

Hom.:

Bravo

AF:

0.0924

Asia WGS

AF:

0.105

AC:

364

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 13, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 22. Only high quality variants are reported. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -

Neuronal ceroid lipofuscinosis 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Neuronal ceroid lipofuscinosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 04, 2025	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.4

DANN

Benign

0.68

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

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