Variant 14-100845451-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 NR_046467.1(MEG3):n.1352-7G>C variant causes a splice region, splice polypyrimidine tract, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 456,600 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 46 hom., cov: 32)

Exomes 𝑓: 0.023 ( 192 hom. )

Consequence

MEG3
NR_046467.1 splice_region, splice_polypyrimidine_tract, intron, non_coding_transcript

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.25

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:

(HGNC:):

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=-0.94).

BP6

Variant 14-100845451-G-C is Benign according to our data. Variant chr14-100845451-G-C is described in ClinVar as [Benign]. Clinvar id is 3056262.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_046467.1 linkuse as main transcript	n.1352-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000554041.1 linkuse as main transcript	n.144-10874C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2637

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00558

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0145

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00952

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0299

AC:

4127

AN:

138068

Hom.:

149

AF XY:

0.0255

AC XY:

1907

AN XY:

74814

show subpopulations

Gnomad AFR exome

AF:

0.00619

Gnomad AMR exome

AF:

0.0946

Gnomad ASJ exome

AF:

0.00965

Gnomad EAS exome

AF:

0.0143

Gnomad SAS exome

AF:

0.00637

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0234

AC:

7132

AN:

304342

Hom.:

192

Cov.:

AF XY:

0.0203

AC XY:

3522

AN XY:

173286

show subpopulations

Gnomad4 AFR exome

AF:

0.00649

Gnomad4 AMR exome

AF:

0.0948

Gnomad4 ASJ exome

AF:

0.00984

Gnomad4 EAS exome

AF:

0.0152

Gnomad4 SAS exome

AF:

0.00623

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0174

AC:

2648

AN:

152258

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1187

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00556

Gnomad4 AMR

AF:

0.0432

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00952

Gnomad4 NFE

AF:

0.0213

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0223

Asia WGS

AF:

0.0210

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 06, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.052

DANN

Benign

0.74

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