14-100852021-G-T

Variant names:

• chr14-100852021-G-T
• rs78555954
• ENST00000649261.2:n.1643+6488G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_046473.1(MEG3):​n.7405G>T 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 0.0000239 in 83,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: MEG3 NR_046473.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 1 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]

ENSG00000258663 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_046473.1. 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
	MEG3	NR_190993.1	MANE Select	n.1643+6488G>T		intron	N/A
	MEG3	NR_046473.1		n.7405G>T		non_coding_transcript_exon	Exon 7 of 7
	MEG3	NR_190994.1		n.7515G>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEG3	ENST00000649261.2	MANE Select	n.1643+6488G>T		intron	N/A
	MEG3	ENST00000398461.6	TSL:1	n.3121+6488G>T		intron	N/A
	MEG3	ENST00000429159.7	TSL:1	n.1275+6488G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000239 AC: 2 AN: 83688 Hom.: 0 Cov.: 0 AF XY: 0.0000220 AC XY: 1 AN XY: 45464

African (AFR) AF: 0.00 AC: 0 AN: 1872

American (AMR) AF: 0.00 AC: 0 AN: 4582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1708

East Asian (EAS) AF: 0.00 AC: 0 AN: 2680

South Asian (SAS) AF: 0.00 AC: 0 AN: 16564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3898

Middle Eastern (MID) AF: 0.00309 AC: 1 AN: 324

European-Non Finnish (NFE) AF: 0.0000209 AC: 1 AN: 47898

Other (OTH) AF: 0.00 AC: 0 AN: 4162

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.6
DANN	Benign	0.83
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs78555954; hg19: chr14-101318358;