14-101066756-C-T

Variant names:

• chr14-101066756-C-T
• rs58834075
• ENST00000385224.1:n.33C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000385224.1(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 ENST00000385224.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MIR656	NR_030392.1	n.33C>T		non_coding_transcript_exon_variant	Exon 1 of 1
MIR656	unassigned_transcript_2453	n.-10C>T		upstream_gene_variant
MIR656	unassigned_transcript_2452	n.*5C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR656	ENST00000385224.1	n.33C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MEG9	ENST00000699461.1	n.497-3686C>T		intron_variant	Intron 4 of 6
MEG9	ENST00000699462.1	n.219+2389C>T		intron_variant	Intron 1 of 3
MEG9	ENST00000818609.1	n.258+2389C>T		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.0462 AC: 11598 AN: 251018 AF XY: 0.0443

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 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

African (AFR) AF: 0.170 AC: 1783 AN: 10512

American (AMR) AF: 0.0454 AC: 1649 AN: 36292

Ashkenazi Jewish (ASJ) AF: 0.00818 AC: 96 AN: 11742

East Asian (EAS) AF: 0.0366 AC: 482 AN: 13176

South Asian (SAS) AF: 0.0641 AC: 4280 AN: 66756

European-Finnish (FIN) AF: 0.0345 AC: 1115 AN: 32312

Middle Eastern (MID) AF: 0.0306 AC: 87 AN: 2844

European-Non Finnish (NFE) AF: 0.0300 AC: 5767 AN: 192062

Other (OTH) AF: 0.0450 AC: 753 AN: 16728

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

African (AFR) AF: 0.168 AC: 6962 AN: 41534

American (AMR) AF: 0.0439 AC: 671 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5180

South Asian (SAS) AF: 0.0658 AC: 318 AN: 4830

European-Finnish (FIN) AF: 0.0295 AC: 313 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1872 AN: 68014

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0375 Hom.: 355

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
PhyloP100		0.51

Splicing

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

Other links and lift over

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