Variant ENST00000398461.5:n.3121+6488G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000398461.5(MEG3):n.3121+6488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00768 in 235,934 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

MEG3
ENST00000398461.5 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.90

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:

ENSG00000258663 (HGNC:):

ENSG00000258663 links:

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

MIR493HG 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=-0.81).

BP6

Variant 14-100852021-G-A is Benign according to our data. Variant chr14-100852021-G-A is described in ClinVar as [Benign]. Clinvar id is 3045679.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1721/152248) while in subpopulation AFR AF= 0.0391 (1624/41532). AF 95% confidence interval is 0.0375. There are 31 homozygotes in gnomad4. There are 803 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MEG3	NR_046473.1 link	n.7405G>A	non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1 link	n.7515G>A	non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1 link	n.7645G>A	non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MEG3	ENST00000398461.5 link	n.3121+6488G>A	intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.6 link	n.1275+6488G>A	intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.6 link	n.1241+6488G>A	intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1711

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00718

GnomAD4 exome

AF:

0.00110

AC:

AN:

83686

Hom.:

Cov.:

AF XY:

0.000814

AC XY:

AN XY:

45462

show subpopulations

Gnomad4 AFR exome

AF:

0.0358

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000835

Gnomad4 OTH exome

AF:

0.00216

GnomAD4 genome

AF:

0.0113

AC:

1721

AN:

152248

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

803

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEG3-related disorder

Benign:1

Jan 28, 2020

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

-0.81

CADD

Benign

DANN

Benign

0.78

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