rs151181

Positions:

• chr16-28479196-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042432.2(CLN3):​c.1057-1319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,140 control chromosomes in the GnomAD database, including 9,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9292 hom., cov: 32)
• Consequence: CLN3 NM_001042432.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

CLN3 (HGNC:2074): (CLN3 lysosomal/endosomal transmembrane protein, battenin) This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLN3	NM_001042432.2	c.1057-1319A>G		intron_variant		ENST00000636147.2	NP_001035897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN3	ENST00000636147.2	c.1057-1319A>G		intron_variant		1	NM_001042432.2	ENSP00000490105	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49076 AN: 152022 Hom.: 9281 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49127 AN: 152140 Hom.: 9292 Cov.: 32 AF XY: 0.323 AC XY: 24014 AN XY: 74356

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.305

Alfa AF: 0.376 Hom.: 20615

Bravo AF: 0.310

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151181; hg19: chr16-28490517;