8-1798784-A-G

Variant names:

• chr8-1798784-A-G
• rs11986414
• ENST00000635855.1:n.543+27187A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000635855.1(KBTBD11-OT1):​n.543+27187A>G 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 0.26 (525 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KBTBD11-OT1 ENST00000635855.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD11-OT1	ENST00000635855.1	n.543+27187A>G		intron_variant	Intron 2 of 29	5		ENSP00000489726.1
CLN8	ENST00000636934.1	c.544-1890A>G		intron_variant	Intron 2 of 2	5		ENSP00000490218.1
KBTBD11-OT1	ENST00000635773.1	n.495+27187A>G		intron_variant	Intron 1 of 27	5		ENSP00000490620.1
KBTBD11-OT1	ENST00000636175.1	n.342+27187A>G		intron_variant	Intron 1 of 6	5		ENSP00000490769.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 2441 AN: 9390 Hom.: 518 Cov.: 0

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.282

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.261 AC: 2455 AN: 9404 Hom.: 525 Cov.: 0 AF XY: 0.270 AC XY: 1317 AN XY: 4878

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.310

Alfa AF: 0.817 Hom.: 20223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.085

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11986414; hg19: chr8-1746950; COSMIC: COSV53502251; COSMIC: COSV53502251;