chr14-101046750-C-T

Variant names:

• chr14-101046750-C-T
• rs12100867
• ENST00000553692.1:n.28+1566C>T

Variant summary

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

The ENST00000553692.1(MEG9):​n.28+1566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,498 control chromosomes in the GnomAD database, including 4,209 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 0.21 (4209 hom., cov: 32)
• Consequence: MEG9 ENST00000553692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

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

MIR381HG (HGNC:20136): (MIR381 host gene)

MIR487B (HGNC:32533): (microRNA 487b) 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR381HG	NR_104192.1	n.28+1566C>T		intron_variant	Intron 1 of 2
MIR487B	NR_030267.1	n.*212C>T		downstream_gene_variant
MIR487B	unassigned_transcript_2417	n.*224C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG9	ENST00000553692.1	n.28+1566C>T		intron_variant	Intron 1 of 2	3
MEG9	ENST00000699460.1	n.1056+1566C>T		intron_variant	Intron 7 of 16
MIR487B	ENST00000385021.3	n.*212C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31230 AN: 151380 Hom.: 4210 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31241 AN: 151498 Hom.: 4209 Cov.: 32 AF XY: 0.214 AC XY: 15859 AN XY: 73978

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.219

Alfa AF: 0.216 Hom.: 1951

Bravo AF: 0.214

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12100867; hg19: chr14-101513087;