14-100829493-G-C

Position:

• chr14-100829493-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NR_046467.1(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 NR_046467.1 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.50

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]

(HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_046467.1	n.679G>C		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000611456.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142460 AN: 152162 Hom.: 66706 Cov.: 33

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: 48 AN: 50 Hom.: 23 Cov.: 0 AF XY: 1.00 AC XY: 26 AN XY: 26

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.: 33 AF XY: 0.938 AC XY: 69815 AN XY: 74462

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

Submissions by phenotype

MEG3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 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	-0.99
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

Other links and lift over

dbSNP: rs941575; hg19: chr14-101295830;