14-101066756-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_030392.1(MIR656):n.33C>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 0.0496 in 534,688 control chromosomes in the GnomAD database, including 1,214 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 0.069 (667 hom., cov: 33)
  • Exomes 𝑓: 0.042 (547 hom.)
• Consequence: MIR656 NR_030392.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

Genes affected

MIR656 (HGNC:32912): (microRNA 656) 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]

MEG9 (HGNC:43874): (maternally expressed 9)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR656	NR_030392.1	n.33C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR656	ENST00000385224.1	n.33C>T		non_coding_transcript_exon_variant	1/1
MEG9	ENST00000699461.1	n.497-3686C>T		intron_variant, non_coding_transcript_variant
MEG9	ENST00000699462.1	n.219+2389C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10471 AN: 152146 Hom.: 666 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0439

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.0295

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0502

GnomAD3 exomes AF: 0.0462 AC: 11598 AN: 251018 Hom.: 494 AF XY: 0.0443 AC XY: 6021 AN XY: 135876

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.0459

Gnomad ASJ exome AF: 0.00756

Gnomad EAS exome AF: 0.0417

Gnomad SAS exome AF: 0.0688

Gnomad FIN exome AF: 0.0339

Gnomad NFE exome AF: 0.0295

Gnomad OTH exome AF: 0.0390

GnomAD4 exome AF: 0.0419 AC: 16012 AN: 382424 Hom.: 547 Cov.: 0 AF XY: 0.0421 AC XY: 9176 AN XY: 217714

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.00818

Gnomad4 EAS exome AF: 0.0366

Gnomad4 SAS exome AF: 0.0641

Gnomad4 FIN exome AF: 0.0345

Gnomad4 NFE exome AF: 0.0300

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0690 AC: 10502 AN: 152264 Hom.: 667 Cov.: 33 AF XY: 0.0687 AC XY: 5118 AN XY: 74468

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.0658

Gnomad4 FIN AF: 0.0295

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0402 Hom.: 147

Bravo AF: 0.0735

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
Cadd	Benign	17
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58834075; hg19: chr14-101533093; COSMIC: COSV62998613;