rs16882131

Variant names:

• chr6-52144135-C-T
• rs16882131
• ENST00000784740.1:n.121-4729C>T

Variant summary

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

The ENST00000784740.1(ENSG00000302165):​n.121-4729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,098 control chromosomes in the GnomAD database, including 5,493 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 0.27 (5493 hom., cov: 32)
• Consequence: ENSG00000302165 ENST00000784740.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 9 publications found

Genes affected

ENSG00000302165 (HGNC:):

MIR206 (HGNC:31584): (microRNA 206) 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. Disruption of the encoded miRNA has been implicated in multiple skeletal muscle disorders, including amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD), as well as in several cancers. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR206	NR_029713.1	n.-214C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302165	ENST00000784740.1	n.121-4729C>T		intron_variant	Intron 1 of 1
MIR206	ENST00000384872.3	n.-214C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40438 AN: 151980 Hom.: 5470 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.266 AC: 40507 AN: 152098 Hom.: 5493 Cov.: 32 AF XY: 0.265 AC XY: 19717 AN XY: 74346

African (AFR) AF: 0.289 AC: 12011 AN: 41498

American (AMR) AF: 0.210 AC: 3204 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3472

East Asian (EAS) AF: 0.161 AC: 832 AN: 5178

South Asian (SAS) AF: 0.290 AC: 1393 AN: 4810

European-Finnish (FIN) AF: 0.264 AC: 2796 AN: 10576

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18369 AN: 67966

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.275 Hom.: 5221

Bravo AF: 0.262

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.53
DANN	Benign	0.29
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs16882131; hg19: chr6-52008933;