Genetic Variant ENST00000398461.5:n.3121+379dupG (chr14-100845906-T-TG) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000398461.5(MEG3):n.3121+379dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 155,842 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 0 hom. )

Consequence

MEG3
ENST00000398461.5 intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.04

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 -9 ACMG points.

BP6

Variant 14-100845906-T-TG is Benign according to our data. Variant chr14-100845906-T-TG is described in ClinVar as [Benign]. Clinvar id is 3044287.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1808/152222) while in subpopulation NFE AF= 0.0183 (1245/67994). AF 95% confidence interval is 0.0175. There are 19 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MEG3	NR_046473.1 link	n.1296dupG	non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1 link	n.1406dupG	non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1 link	n.1536dupG	non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MEG3	ENST00000398461.5 link	n.3121+379dupG	intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.6 link	n.1275+379dupG	intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.6 link	n.1241+379dupG	intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1811

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00718

AC:

AN:

3620

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

AN XY:

1948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00193

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00965

Gnomad4 OTH exome

AF:

0.00694

GnomAD4 genome

AF:

0.0119

AC:

1808

AN:

152222

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

842

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00342

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00851

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00404

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 08, 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

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