rs8013873

Positions:

• chr14-100835753-C-T

Variant summary

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

The NR_046467.1(MEG3):​n.1218-414C>T 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 0.171 in 174,500 control chromosomes in the GnomAD database, including 2,786 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 0.18 (2501 hom., cov: 32)
  • Exomes 𝑓: 0.14 (285 hom.)
• Consequence: MEG3 NR_046467.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_046467.1	n.1218-414C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000554041.1	n.144-1176G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26691 AN: 152088 Hom.: 2502 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.144 AC: 3205 AN: 22294 Hom.: 285 Cov.: 0 AF XY: 0.139 AC XY: 1607 AN XY: 11592

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.175 AC: 26693 AN: 152206 Hom.: 2501 Cov.: 32 AF XY: 0.171 AC XY: 12723 AN XY: 74396

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.179

Alfa AF: 0.175 Hom.: 471

Bravo AF: 0.178

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.073
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8013873; hg19: chr14-101302090;