chr14-101059844-G-A

Variant names:

• chr14-101059844-G-A
• rs41286572
• ENST00000699461.1:n.382-1649G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699461.1(MEG9):​n.382-1649G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699461.1. 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
	MIR154	NR_029704.1		n.*6G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEG9	ENST00000699461.1		n.382-1649G>A		intron	N/A
	MIR154	ENST00000385243.1	TSL:6	n.*6G>A		downstream_gene	N/A

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

GnomAD2 exomes AF: 0.0628 AC: 15742 AN: 250856 AF XY: 0.0640

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 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

African (AFR) AF: 0.0274 AC: 288 AN: 10508

American (AMR) AF: 0.0326 AC: 1184 AN: 36292

Ashkenazi Jewish (ASJ) AF: 0.0555 AC: 651 AN: 11724

East Asian (EAS) AF: 0.0310 AC: 408 AN: 13172

South Asian (SAS) AF: 0.0558 AC: 3722 AN: 66724

European-Finnish (FIN) AF: 0.0992 AC: 3206 AN: 32304

Middle Eastern (MID) AF: 0.0862 AC: 242 AN: 2806

European-Non Finnish (NFE) AF: 0.0778 AC: 14936 AN: 191928

Other (OTH) AF: 0.0707 AC: 1181 AN: 16712

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

African (AFR) AF: 0.0276 AC: 1147 AN: 41562

American (AMR) AF: 0.0586 AC: 896 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 217 AN: 3468

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5178

South Asian (SAS) AF: 0.0553 AC: 266 AN: 4814

European-Finnish (FIN) AF: 0.0990 AC: 1049 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5227 AN: 68018

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0603 Hom.: 157

Bravo AF: 0.0554

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		-0.071

Splicing

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

Other links and lift over

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