rs72631832

Variant names:

• chr14-100307866-C-T
• rs72631832
• ENST00000362114.1:n.8C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_029906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR345	NR_029906.1		n.8C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR345	ENST00000362114.1	TSL:6	n.8C>T		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.0166 AC: 2559 AN: 153974 AF XY: 0.0173

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 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

African (AFR) AF: 0.00449 AC: 37 AN: 8232

American (AMR) AF: 0.00718 AC: 187 AN: 26030

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 154 AN: 9956

East Asian (EAS) AF: 0.00 AC: 0 AN: 9016

South Asian (SAS) AF: 0.0119 AC: 689 AN: 57724

European-Finnish (FIN) AF: 0.0283 AC: 781 AN: 27566

Middle Eastern (MID) AF: 0.00784 AC: 21 AN: 2680

European-Non Finnish (NFE) AF: 0.0250 AC: 3593 AN: 143502

Other (OTH) AF: 0.0181 AC: 234 AN: 12950

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

African (AFR) AF: 0.00385 AC: 160 AN: 41582

American (AMR) AF: 0.0100 AC: 153 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4828

European-Finnish (FIN) AF: 0.0292 AC: 310 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0254 AC: 1727 AN: 68016

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.0
DANN	Benign	0.70
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs72631832; hg19: chr14-100774203;