rs41286572

chr14-101059844-G-Achr14-101059844-G-Cchr14-101059844-G-T

Variant summary

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

The ENST00000699461.1(MEG9):n.382-1649G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 534,412 control chromosomes in the GnomAD database, including 1,381 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 0.061 (342 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1039 hom.)
• Consequence: MEG9 ENST00000699461.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

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

MIR154 (HGNC:31541): (microRNA 154) 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=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR154	NR_029704.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEG9	ENST00000699461.1	n.382-1649G>A		intron_variant, non_coding_transcript_variant
MIR154	ENST00000385243.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9289 AN: 152124 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.0670

GnomAD3 exomes AF: 0.0628 AC: 15742 AN: 250856 Hom.: 605 AF XY: 0.0640 AC XY: 8695 AN XY: 135790

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.0328

Gnomad ASJ exome AF: 0.0558

Gnomad EAS exome AF: 0.0303

Gnomad SAS exome AF: 0.0555

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.0776

Gnomad OTH exome AF: 0.0649

GnomAD4 exome AF: 0.0676 AC: 25818 AN: 382170 Hom.: 1039 Cov.: 0 AF XY: 0.0677 AC XY: 14730 AN XY: 217556

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0326

Gnomad4 ASJ exome AF: 0.0555

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.0558

Gnomad4 FIN exome AF: 0.0992

Gnomad4 NFE exome AF: 0.0778

Gnomad4 OTH exome AF: 0.0707

GnomAD4 genome AF: 0.0610 AC: 9290 AN: 152242 Hom.: 342 Cov.: 32 AF XY: 0.0614 AC XY: 4567 AN XY: 74436

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.0586

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0607 Hom.: 157

Bravo AF: 0.0554

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	14
Dann	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41286572; hg19: chr14-101526181; COSMIC: COSV62998895;