Genetic Variant KBTBD11-OT1:n.544-26148G>T (chr8-1817205-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000635855.1(KBTBD11-OT1):n.544-26148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 336,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

KBTBD11-OT1
ENST00000635855.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

0 publications found

Variant links:

Genes affected

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

MIR596 (HGNC:32852): (microRNA 596) 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]

MIR596 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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
	MIR596	NR_030326.1		n.-26G>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KBTBD11-OT1	ENST00000635855.1	TSL:5	n.544-26148G>T	intron	N/A	ENSP00000489726.1	A0A1B0GTJ5
KBTBD11-OT1	ENST00000635773.1	TSL:5	n.496-40755G>T	intron	N/A	ENSP00000490620.1	A0A1B0GVR1
KBTBD11-OT1	ENST00000636175.1	TSL:5	n.343-26148G>T	intron	N/A	ENSP00000490769.1	A0A1B0GW43

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000297

AC:

AN:

336204

Hom.:

Cov.:

AF XY:

0.00000531

AC XY:

AN XY:

188498

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

9240

American (AMR)

AF:

0.00

AC:

AN:

32192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10576

East Asian (EAS)

AF:

0.00

AC:

AN:

11074

South Asian (SAS)

AF:

0.00

AC:

AN:

62032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2714

European-Non Finnish (NFE)

AF:

0.00000616

AC:

AN:

162254

Other (OTH)

AF:

0.00

AC:

AN:

14552

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

(source)

DANN

Benign

0.31

PhyloP100

0.51

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over