rs12894467

Positions:

• chr14-101041390-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_030582.1(MIR300):​n.28C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 533,582 control chromosomes in the GnomAD database, including 68,634 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 0.51 (20245 hom., cov: 32)
  • Exomes 𝑓: 0.49 (48389 hom.)
• Consequence: MIR300 NR_030582.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

Genes affected

MIR300 (HGNC:33636): (microRNA 300) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR300	NR_030582.1	n.28C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR300	ENST00000401138.1	n.28C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76841 AN: 151932 Hom.: 20221 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.508

GnomAD3 exomes AF: 0.511 AC: 127914 AN: 250308 Hom.: 34489 AF XY: 0.505 AC XY: 68426 AN XY: 135508

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.771

Gnomad SAS exome AF: 0.572

Gnomad FIN exome AF: 0.504

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.492 AC: 187710 AN: 381532 Hom.: 48389 Cov.: 0 AF XY: 0.493 AC XY: 107163 AN XY: 217228

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.618

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.506 AC: 76917 AN: 152050 Hom.: 20245 Cov.: 32 AF XY: 0.513 AC XY: 38105 AN XY: 74314

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.507

Alfa AF: 0.454 Hom.: 7000

Bravo AF: 0.513

Asia WGS AF: 0.671 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12894467; hg19: chr14-101507727; COSMIC: COSV62999658;