14-100851454-G-A

Variant names:

• chr14-100851454-G-A
• rs3783357
• ENST00000398461.5:n.3121+5921G>A

Variant summary

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

The NR_046473.1(MEG3):​n.6838G>A 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 0.262 in 152,142 control chromosomes in the GnomAD database, including 6,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (6034 hom., cov: 32)
  • Exomes 𝑓: 0.37 (14 hom.)
• Consequence: MEG3 NR_046473.1 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.484

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]

ENSG00000258663 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-100851454-G-A is Benign according to our data. Variant chr14-100851454-G-A is described in ClinVar as [Benign]. Clinvar id is 3060854.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_046473.1	n.6838G>A		non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1	n.6948G>A		non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1	n.7078G>A		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.3121+5921G>A		intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.6	n.1275+5921G>A		intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.6	n.1241+5921G>A		intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39878 AN: 151878 Hom.: 6042 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.370 AC: 54 AN: 146 Hom.: 14 Cov.: 0 AF XY: 0.385 AC XY: 40 AN XY: 104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.262 AC: 39875 AN: 151996 Hom.: 6034 Cov.: 32 AF XY: 0.265 AC XY: 19676 AN XY: 74292

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.251

Alfa AF: 0.310 Hom.: 1874

Bravo AF: 0.253

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Jul 03, 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	-0.83
CADD	Benign	6.0
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3783357; hg19: chr14-101317791;