chr14-100809613-G-A

Variant names:

• chr14-100809613-G-A
• rs12437020
• ENST00000556407.5:n.372-19095G>A

Variant summary

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

The ENST00000556407.5(MEG3):​n.372-19095G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,006 control chromosomes in the GnomAD database, including 5,488 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 0.26 (5488 hom., cov: 32)
• Consequence: MEG3 ENST00000556407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 10 publications found

Genes affected

MEG3 (HGNC:14575): (maternally expressed 3) This gene is a maternally expressed imprinted gene. Multiple alternatively spliced transcript variants have been transcribed from this gene and all of them are long non-coding RNAs (lncRNAs). This gene is expressed in many normal tissues, but its expression is lost in multiple cancer cell lines of various tissue origins. It inhibits tumor cell proliferation in vitro. It also interacts with the tumor suppressor p53, and regulates p53 target gene expression. Its deletion enhances angiogenesis in vivo. Many experimental evidences demonstrate that this gene is a lncRNA tumor suppressor. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000556407.5	n.372-19095G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39653 AN: 151888 Hom.: 5482 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.261 AC: 39684 AN: 152006 Hom.: 5488 Cov.: 32 AF XY: 0.267 AC XY: 19823 AN XY: 74278

African (AFR) AF: 0.185 AC: 7658 AN: 41462

American (AMR) AF: 0.293 AC: 4479 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2053 AN: 5140

South Asian (SAS) AF: 0.318 AC: 1529 AN: 4814

European-Finnish (FIN) AF: 0.311 AC: 3274 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18703 AN: 67984

Other (OTH) AF: 0.270 AC: 571 AN: 2116

Alfa AF: 0.274 Hom.: 18575

Bravo AF: 0.259

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.63
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs12437020; hg19: chr14-101275950;