8-1817205-G-C

Variant names:

• chr8-1817205-G-C
• rs6980781
• ENST00000635855.1:n.544-26148G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000635855.1(KBTBD11-OT1):​n.544-26148G>C 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 8 publications found

Genes affected

KBTBD11-OT1 (HGNC:):

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]

ACMG classification

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR596	NR_030326.1	n.-26G>C		upstream_gene_variant
MIR596	unassigned_transcript_1436	n.-41G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD11-OT1	ENST00000635855.1	n.544-26148G>C		intron_variant	Intron 2 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000297 AC: 1 AN: 336204 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 188498

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

African (AFR) AF: 0.00 AC: 0 AN: 9240

American (AMR) AF: 0.00 AC: 0 AN: 32192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10576

East Asian (EAS) AF: 0.00 AC: 0 AN: 11074

South Asian (SAS) AF: 0.00 AC: 0 AN: 62032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2714

European-Non Finnish (NFE) AF: 0.00000616 AC: 1 AN: 162254

Other (OTH) AF: 0.00 AC: 0 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.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.13
PhyloP100		0.51

Splicing

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

Other links and lift over

dbSNP: rs6980781; hg19: chr8-1765371;