chr14-100850603-CAAAAAAGA-C

Position:

• chr14-100850603-CAAAAAAGA-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NR_046467.1(MEG3):​n.1427+5077_1427+5084del variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEG3 NR_046467.1 intron, non_coding_transcript
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0560

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 Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 14-100850603-CAAAAAAGA-C is Benign according to our data. Variant chr14-100850603-CAAAAAAGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035333.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_046467.1	n.1427+5077_1427+5084del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000554041.1	n.143+10273_143+10280del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000735 AC: 72 AN: 97978 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000762

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000271

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000739

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000735 AC: 72 AN: 98012 Hom.: 1 Cov.: 0 AF XY: 0.000651 AC XY: 31 AN XY: 47642

Gnomad4 AFR AF: 0.000181

Gnomad4 AMR AF: 0.000761

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000272

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.000735

Alfa AF: 0.00135 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1274309643; hg19: chr14-101316940;