chr14-100845906-T-TG

Variant names:

• chr14-100845906-T-TG
• rs200608518
• ENST00000398461.5:n.3121+379dupG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000455531.1(MEG3):​n.3478dupG 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 0.0118 in 155,842 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (0 hom.)
• Consequence: MEG3 ENST00000455531.1 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.04

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

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 14-100845906-T-TG is Benign according to our data. Variant chr14-100845906-T-TG is described in ClinVar as [Benign]. Clinvar id is 3044287.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1808/152222) while in subpopulation NFE AF= 0.0183 (1245/67994). AF 95% confidence interval is 0.0175. There are 19 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_046473.1	n.1296dupG		non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1	n.1406dupG		non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1	n.1536dupG		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.3121+379dupG		intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.6	n.1275+379dupG		intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.6	n.1241+379dupG		intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1811 AN: 152104 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00718 AC: 26 AN: 3620 Hom.: 0 Cov.: 0 AF XY: 0.00513 AC XY: 10 AN XY: 1948

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00965

Gnomad4 OTH exome AF: 0.00694

GnomAD4 genome AF: 0.0119 AC: 1808 AN: 152222 Hom.: 19 Cov.: 32 AF XY: 0.0113 AC XY: 842 AN XY: 74434

Gnomad4 AFR AF: 0.00342

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0128

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0129 Hom.: 2

Bravo AF: 0.0116

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Jan 08, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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: rs200608518; hg19: chr14-101312243;