chr8-1817205-G-A

Variant names:

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

Variant summary

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

The ENST00000635855.1(KBTBD11-OT1):​n.544-26148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 488,014 control chromosomes in the GnomAD database, including 6,551 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 0.16 (2307 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4244 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23972 AN: 152062 Hom.: 2302 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.136 AC: 30636 AN: 224744 AF XY: 0.141

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.0638

Gnomad ASJ exome AF: 0.0681

Gnomad EAS exome AF: 0.124

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.140 AC: 47130 AN: 335834 Hom.: 4244 Cov.: 0 AF XY: 0.151 AC XY: 28434 AN XY: 188292

African (AFR) AF: 0.263 AC: 2426 AN: 9214

American (AMR) AF: 0.0641 AC: 2062 AN: 32170

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 690 AN: 10572

East Asian (EAS) AF: 0.122 AC: 1346 AN: 11052

South Asian (SAS) AF: 0.253 AC: 15655 AN: 61938

European-Finnish (FIN) AF: 0.180 AC: 5687 AN: 31540

Middle Eastern (MID) AF: 0.132 AC: 359 AN: 2712

European-Non Finnish (NFE) AF: 0.105 AC: 17081 AN: 162108

Other (OTH) AF: 0.126 AC: 1824 AN: 14528

GnomAD4 genome AF: 0.158 AC: 24012 AN: 152180 Hom.: 2307 Cov.: 33 AF XY: 0.163 AC XY: 12102 AN XY: 74410

African (AFR) AF: 0.262 AC: 10866 AN: 41484

American (AMR) AF: 0.0970 AC: 1484 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0623 AC: 216 AN: 3468

East Asian (EAS) AF: 0.131 AC: 676 AN: 5166

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4824

European-Finnish (FIN) AF: 0.184 AC: 1954 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7145 AN: 68014

Other (OTH) AF: 0.137 AC: 289 AN: 2110

Alfa AF: 0.113 Hom.: 2359

Bravo AF: 0.150

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.67
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; COSMIC: COSV66089055;