Variant 14-100831030-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000398474.7(MEG3):n.426G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 152,826 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 0 hom. )

Consequence

MEG3
ENST00000398474.7 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.87

Variant links:

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]

MEG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 14-100831030-G-T is Benign according to our data. Variant chr14-100831030-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644539.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
MEG3	NR_033359.1 link	n.950G>T	non_coding_transcript_exon_variant	4/8
MEG3	NR_002766.2 link	n.936-391G>T	intron_variant
MEG3	NR_003530.2 link	n.936-391G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
MEG3	ENST00000429159.6 link	n.935+1281G>T	intron_variant	1
MEG3	ENST00000451743.6 link	n.918-391G>T	intron_variant	1
MEG3	ENST00000521404.5 link	n.917+1281G>T	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

778

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00723

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00581

AC:

AN:

516

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

AN XY:

294

show subpopulations

Gnomad4 FIN exome

AF:

0.00431

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00511

AC:

778

AN:

152310

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

369

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00723

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00603

Hom.:

Bravo

AF:

0.00582

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MEG3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

MEG3: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.81

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over