chr14-100824126-C-A

Position:

• chr14-100824126-C-A

Variant summary

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

The ENST00000556407.5(MEG3):​n.372-4582C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,144 control chromosomes in the GnomAD database, including 6,870 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 0.28 (6870 hom., cov: 33)
• Consequence: MEG3 ENST00000556407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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

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 = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000556407.5	n.372-4582C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43211 AN: 152026 Hom.: 6864 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.284 AC: 43260 AN: 152144 Hom.: 6870 Cov.: 33 AF XY: 0.295 AC XY: 21942 AN XY: 74370

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.309

Alfa AF: 0.148 Hom.: 303

Bravo AF: 0.288

Asia WGS AF: 0.492 AC: 1715 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	1.9
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11627993; hg19: chr14-101290463;