rs1054013

Positions:

• chr14-100846532-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_046467.1(MEG3):​n.1427+999G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,262 control chromosomes in the GnomAD database, including 5,943 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5942 hom., cov: 33)
  • Exomes 𝑓: 0.28 (1 hom.)
• Consequence: MEG3 NR_046467.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_046467.1	n.1427+999G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000554041.1	n.144-11955C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39140 AN: 152098 Hom.: 5951 Cov.: 33

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.283 AC: 13 AN: 46 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 10 AN XY: 30

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.257 AC: 39124 AN: 152216 Hom.: 5942 Cov.: 33 AF XY: 0.259 AC XY: 19288 AN XY: 74410

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.247

Alfa AF: 0.316 Hom.: 13079

Bravo AF: 0.248

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1054013; hg19: chr14-101312869;