rs7003112

Positions:

• chr8-1801244-T-A

Variant summary

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

The ENST00000636934.1(CLN8):​c.*463T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 154,730 control chromosomes in the GnomAD database, including 37,754 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 0.70 (37108 hom., cov: 33)
  • Exomes 𝑓: 0.70 (646 hom.)
• Consequence: CLN8 ENST00000636934.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

CLN8 (HGNC:2079): (CLN8 transmembrane ER and ERGIC protein) This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with a disorder characterized by progressive epilepsy with cognitive disabilities (EPMR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 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
CLN8	ENST00000636934.1	c.*463T>A		3_prime_UTR_variant	3/3	5		ENSP00000490218
CLN8	ENST00000636605.1	n.602T>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105784 AN: 152010 Hom.: 37092 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.696 AC: 1811 AN: 2602 Hom.: 646 Cov.: 0 AF XY: 0.686 AC XY: 935 AN XY: 1362

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.696 AC: 105844 AN: 152128 Hom.: 37108 Cov.: 33 AF XY: 0.688 AC XY: 51152 AN XY: 74344

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.729

Alfa AF: 0.708 Hom.: 3567

Bravo AF: 0.689

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7003112; hg19: chr8-1749410;