rs654196

Positions:

• chr13-76991837-A-G

Variant summary

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

The ENST00000636183.2(CLN5):​c.-262A>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 0.586 in 1,328,844 control chromosomes in the GnomAD database, including 243,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (20541 hom., cov: 32)
  • Exomes 𝑓: 0.60 (222841 hom.)
• Consequence: CLN5 ENST00000636183.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.412

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=-0.79).
• BP6: Variant 13-76991837-A-G is Benign according to our data. Variant chr13-76991837-A-G is described in ClinVar as [Benign]. Clinvar id is 670727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN5	ENST00000636183.2	c.-262A>G		5_prime_UTR_variant	1/4	1		ENSP00000490181	P1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71043 AN: 151988 Hom.: 20542 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.602 AC: 707938 AN: 1176738 Hom.: 222841 Cov.: 17 AF XY: 0.598 AC XY: 352312 AN XY: 589576

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.467 AC: 71038 AN: 152106 Hom.: 20541 Cov.: 32 AF XY: 0.463 AC XY: 34406 AN XY: 74354

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.516

Alfa AF: 0.566 Hom.: 11304

Bravo AF: 0.442

Asia WGS AF: 0.296 AC: 1030 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	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs654196; hg19: chr13-77565972;