Variant chr14-100829493-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000429159.6(MEG3):n.679G>C 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 0.936 in 152,330 control chromosomes in the GnomAD database, including 66,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.94 ( 66758 hom., cov: 33)

Exomes 𝑓: 0.96 ( 23 hom. )

Consequence

MEG3
ENST00000429159.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.50

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:

ENSG00000276919 (HGNC:):

ENSG00000276919 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 14-100829493-G-C is Benign according to our data. Variant chr14-100829493-G-C is described in ClinVar as [Benign]. Clinvar id is 3059566.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MEG3	NR_002766.2 link	n.679G>C	non_coding_transcript_exon_variant	Exon 3 of 7
MEG3	NR_003530.2 link	n.679G>C	non_coding_transcript_exon_variant	Exon 3 of 9
MEG3	NR_003531.3 link	n.655G>C	non_coding_transcript_exon_variant	Exon 3 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MEG3	ENST00000429159.6 link	n.679G>C	non_coding_transcript_exon_variant	Exon 3 of 7	1
MEG3	ENST00000451743.6 link	n.661G>C	non_coding_transcript_exon_variant	Exon 3 of 7	1
MEG3	ENST00000521404.5 link	n.661G>C	non_coding_transcript_exon_variant	Exon 3 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142460

AN:

152162

Hom.:

66706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.940

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.943

Gnomad ASJ

AF:

0.933

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.978

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.955

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.939

GnomAD4 exome

AF:

0.960

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.952

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.936

AC:

142570

AN:

152280

Hom.:

66758

Cov.:

AF XY:

0.938

AC XY:

69815

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.940

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.933

Gnomad4 EAS

AF:

0.977

Gnomad4 SAS

AF:

0.978

Gnomad4 FIN

AF:

0.943

Gnomad4 NFE

AF:

0.925

Gnomad4 OTH

AF:

0.939

Alfa

AF:

0.928

Hom.:

7629

Bravo

AF:

0.936

Asia WGS

AF:

0.979

AC:

3400

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEG3-related disorder

Benign:1

Aug 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.56

DANN

Benign

0.39

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