chr8-1798230-G-T

Variant names:

• chr8-1798230-G-T
• rs138685580
• ENST00000635855.1:n.543+26633G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635855.1(KBTBD11-OT1):​n.543+26633G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 (21809 hom., cov: 13)
• Consequence: KBTBD11-OT1 ENST00000635855.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 0 publications found

Genes affected

KBTBD11-OT1 (HGNC:):

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 Gene-Disease associations (from GenCC):

• neuronal ceroid lipofuscinosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• neuronal ceroid lipofuscinosis 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Myriad Women’s Health
• neuronal ceroid lipofuscinosis 8 northern epilepsy variant

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635855.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD11-OT1	ENST00000635855.1	TSL:5	n.543+26633G>T		intron	N/A	ENSP00000489726.1
	CLN8	ENST00000636934.1	TSL:5	c.544-2444G>T		intron	N/A	ENSP00000490218.1
	KBTBD11-OT1	ENST00000635773.1	TSL:5	n.495+26633G>T		intron	N/A	ENSP00000490620.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 62104 AN: 89046 Hom.: 21798 Cov.: 13

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.697 AC: 62141 AN: 89122 Hom.: 21809 Cov.: 13 AF XY: 0.693 AC XY: 29705 AN XY: 42866

African (AFR) AF: 0.637 AC: 15191 AN: 23864

American (AMR) AF: 0.565 AC: 5588 AN: 9882

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 1584 AN: 2212

East Asian (EAS) AF: 0.584 AC: 1772 AN: 3032

South Asian (SAS) AF: 0.691 AC: 1782 AN: 2578

European-Finnish (FIN) AF: 0.761 AC: 3593 AN: 4724

Middle Eastern (MID) AF: 0.727 AC: 144 AN: 198

European-Non Finnish (NFE) AF: 0.762 AC: 31200 AN: 40938

Other (OTH) AF: 0.709 AC: 837 AN: 1180

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs138685580; hg19: chr8-1746396; COSMIC: COSV51807541; COSMIC: COSV51807541;