rs941576

chr14-100839708-A-Gchr14-100839708-A-T

Variant summary

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

The NR_046467.1(MEG3):n.1351+3408A>G 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 0.445 in 151,982 control chromosomes in the GnomAD database, including 15,283 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 0.44 (15283 hom., cov: 32)
• Consequence: MEG3 NR_046467.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755

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 (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEG3	NR_046467.1	n.1351+3408A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000554041.1	n.144-5131T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67564 AN: 151864 Hom.: 15278 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67613 AN: 151982 Hom.: 15283 Cov.: 32 AF XY: 0.443 AC XY: 32927 AN XY: 74258

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.442

Alfa AF: 0.439 Hom.: 3123

Bravo AF: 0.446

Asia WGS AF: 0.303 AC: 1051 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	2.4
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs941576; hg19: chr14-101306045;