rs7003112

Variant names:

• chr8-1801244-T-A
• rs7003112
• ENST00000635855.1:n.543+29647T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-1801244-T-A
• chr8-1801244-T-G

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+29647T>A variant causes a intron 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: KBTBD11-OT1 ENST00000635855.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 5 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]

MIR3674 (HGNC:38915): (microRNA 3674) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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.

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
	MIR3674	NR_037445.1		n.*52T>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KBTBD11-OT1	ENST00000635855.1	TSL:5	n.543+29647T>A		intron	N/A	ENSP00000489726.1	A0A1B0GTJ5
	CLN8	ENST00000636934.1	TSL:5	c.*463T>A		3_prime_UTR	Exon 3 of 3	ENSP00000490218.1	A0A1B0GUR8
	CLN8	ENST00000636605.1	TSL:5	n.602T>A		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.625 AC: 50 AN: 80

American (AMR) AF: 0.333 AC: 2 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.400 AC: 4 AN: 10

South Asian (SAS) AF: 0.587 AC: 54 AN: 92

European-Finnish (FIN) AF: 0.714 AC: 300 AN: 420

Middle Eastern (MID) AF: 0.709 AC: 1154 AN: 1628

European-Non Finnish (NFE) AF: 0.661 AC: 115 AN: 174

Other (OTH) AF: 0.688 AC: 128 AN: 186

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

African (AFR) AF: 0.671 AC: 27814 AN: 41480

American (AMR) AF: 0.616 AC: 9414 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2575 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3083 AN: 5164

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4822

European-Finnish (FIN) AF: 0.684 AC: 7235 AN: 10584

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50425 AN: 68002

Other (OTH) AF: 0.729 AC: 1540 AN: 2112

Alfa AF: 0.723 Hom.: 4986

Bravo AF: 0.689

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs7003112; hg19: chr8-1749410; COSMIC: COSV107188718; COSMIC: COSV107188718;