Variant chr8-1763883-C-T 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 NM_018941.4(CLN8):c.-126C>T variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,076 control chromosomes in the GnomAD database, including 441 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 440 hom., cov: 28)

Exomes 𝑓: 0.068 ( 1 hom. )

Consequence

CLN8
NM_018941.4 splice_region, 5_prime_UTR

Scores

Splicing: ADA: 0.001860

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.120

Variant links:

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]

CLN8 links:

CLN8-AS1 (HGNC:55523): (CLN8 antisense RNA 1)

CLN8-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 8-1763883-C-T is Benign according to our data. Variant chr8-1763883-C-T is described in ClinVar as [Benign]. Clinvar id is 136808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLN8	NM_018941.4 linkuse as main transcript	c.-126C>T		splice_region_variant, 5_prime_UTR_variant	1/3	ENST00000331222.6
CLN8-AS1	NR_134303.1 linkuse as main transcript	n.151+551G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLN8	ENST00000331222.6 linkuse as main transcript	c.-126C>T		splice_region_variant, 5_prime_UTR_variant	1/3	1	NM_018941.4	P1
CLN8-AS1	ENST00000659375.1 linkuse as main transcript	n.75+551G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9800

AN:

150900

Hom.:

441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.0457

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.0425

Gnomad NFE

AF:

0.0776

Gnomad OTH

AF:

0.0551

GnomAD4 exome

AF:

0.0675

AC:

AN:

1066

Hom.:

Cov.:

AF XY:

0.0625

AC XY:

AN XY:

800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.0854

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0645

Gnomad4 OTH exome

AF:

0.0652

GnomAD4 genome

AF:

0.0649

AC:

9796

AN:

151010

Hom.:

440

Cov.:

AF XY:

0.0700

AC XY:

5167

AN XY:

73792

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.0330

Gnomad4 ASJ

AF:

0.0457

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.0776

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0642

Hom.:

Bravo

AF:

0.0536

Asia WGS

AF:

0.160

AC:

552

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2013

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

-0.69

CADD

Benign

7.3

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.10

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