rs112141862

Positions:

• chr13-76992289-C-T

Variant summary

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

The NM_006493.4(CLN5):​c.173+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,541,536 control chromosomes in the GnomAD database, including 1,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (407 hom., cov: 32)
  • Exomes 𝑓: 0.025 (777 hom.)
• Consequence: CLN5 NM_006493.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.523

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-76992289-C-T is Benign according to our data. Variant chr13-76992289-C-T is described in ClinVar as [Benign]. Clinvar id is 95397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-76992289-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN5	NM_006493.4	c.173+18C>T		intron_variant		ENST00000377453.9	NP_006484.2
CLN5	NM_001366624.2	c.173+18C>T		intron_variant			NP_001353553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000377453.9	c.173+18C>T		intron_variant		1	NM_006493.4	ENSP00000366673	P1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8461 AN: 151502 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0407

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0509

GnomAD3 exomes AF: 0.0379 AC: 5243 AN: 138422 Hom.: 145 AF XY: 0.0349 AC XY: 2676 AN XY: 76636

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.0408

Gnomad EAS exome AF: 0.0702

Gnomad SAS exome AF: 0.0116

Gnomad FIN exome AF: 0.0577

Gnomad NFE exome AF: 0.0274

Gnomad OTH exome AF: 0.0348

GnomAD4 exome AF: 0.0252 AC: 35051 AN: 1389920 Hom.: 777 Cov.: 34 AF XY: 0.0248 AC XY: 17064 AN XY: 687406

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0364

Gnomad4 ASJ exome AF: 0.0377

Gnomad4 EAS exome AF: 0.0565

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0548

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0343

GnomAD4 genome AF: 0.0560 AC: 8484 AN: 151616 Hom.: 407 Cov.: 32 AF XY: 0.0566 AC XY: 4191 AN XY: 74070

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0407

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0504

Alfa AF: 0.0441 Hom.: 59

Bravo AF: 0.0580

Asia WGS AF: 0.0430 AC: 153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:8

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 12, 2022	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2013	- -
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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 19, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuronal ceroid lipofuscinosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.91

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: rs112141862; hg19: chr13-77566424;