rs72631832

Positions:

• chr14-100307866-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_029906.1(MIR345):​n.8C>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 0.0182 in 449,978 control chromosomes in the GnomAD database, including 97 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 0.016 (27 hom., cov: 33)
  • Exomes 𝑓: 0.019 (70 hom.)
• Consequence: MIR345 NR_029906.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

MIR345 (HGNC:31779): (microRNA 345) 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=-0.61).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2495/152322) while in subpopulation NFE AF= 0.0254 (1727/68016). AF 95% confidence interval is 0.0244. There are 27 homozygotes in gnomad4. There are 1192 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR345	NR_029906.1	n.8C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR345	ENST00000362114.1	n.8C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2495 AN: 152204 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0166 AC: 2559 AN: 153974 Hom.: 28 AF XY: 0.0173 AC XY: 1405 AN XY: 81272

Gnomad AFR exome AF: 0.00429

Gnomad AMR exome AF: 0.00760

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.000179

Gnomad SAS exome AF: 0.0116

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0245

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0191 AC: 5696 AN: 297656 Hom.: 70 Cov.: 0 AF XY: 0.0188 AC XY: 3191 AN XY: 169374

Gnomad4 AFR exome AF: 0.00449

Gnomad4 AMR exome AF: 0.00718

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.0283

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.0181

GnomAD4 genome AF: 0.0164 AC: 2495 AN: 152322 Hom.: 27 Cov.: 33 AF XY: 0.0160 AC XY: 1192 AN XY: 74478

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.0292

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0211 Hom.: 21

Bravo AF: 0.0138

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.0
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72631832; hg19: chr14-100774203;