14-100785652-C-T

Variant names:

• chr14-100785652-C-T
• rs1884537
• ENST00000556407.5:n.371+5872C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556407.5(MEG3):​n.371+5872C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,068 control chromosomes in the GnomAD database, including 11,287 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 0.37 (11287 hom., cov: 33)
• Consequence: MEG3 ENST00000556407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEG3	ENST00000556407.5	TSL:4	n.371+5872C>T		intron	N/A
	MEG3	ENST00000824814.1		n.576-3910C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56787 AN: 151950 Hom.: 11283 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.374 AC: 56815 AN: 152068 Hom.: 11287 Cov.: 33 AF XY: 0.375 AC XY: 27864 AN XY: 74322

African (AFR) AF: 0.250 AC: 10352 AN: 41472

American (AMR) AF: 0.349 AC: 5335 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1733 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2032 AN: 5158

South Asian (SAS) AF: 0.434 AC: 2088 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4577 AN: 10558

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29370 AN: 67990

Other (OTH) AF: 0.395 AC: 833 AN: 2108

Alfa AF: 0.409 Hom.: 42119

Bravo AF: 0.365

Asia WGS AF: 0.441 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.67
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs1884537; hg19: chr14-101251989;