rs138219395

Variant names:

• chr14-100836270-G-A
• rs138219395
• ENST00000398461.5:n.3015G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The ENST00000398461.5(MEG3):​n.3015G>A 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 0.0019 in 456,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (0 hom.)
• Consequence: MEG3 ENST00000398461.5 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.15

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]

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

ENSG00000258663 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-100836270-G-A is Benign according to our data. Variant chr14-100836270-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034727.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_002766.2	n.1153G>A		non_coding_transcript_exon_variant	Exon 5 of 7
MEG3	NR_003530.2	n.1403G>A		non_coding_transcript_exon_variant	Exon 7 of 9
MEG3	NR_003531.3	n.1270G>A		non_coding_transcript_exon_variant	Exon 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.3015G>A		non_coding_transcript_exon_variant	Exon 2 of 4	1
MEG3	ENST00000429159.6	n.1169G>A		non_coding_transcript_exon_variant	Exon 5 of 7	1
MEG3	ENST00000451743.6	n.1135G>A		non_coding_transcript_exon_variant	Exon 5 of 7	1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00322

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00197 AC: 275 AN: 139280 Hom.: 0 AF XY: 0.00183 AC XY: 138 AN XY: 75512

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000445

Gnomad FIN exome AF: 0.000288

Gnomad NFE exome AF: 0.00278

Gnomad OTH exome AF: 0.00666

GnomAD4 exome AF: 0.00202 AC: 615 AN: 304276 Hom.: 0 Cov.: 0 AF XY: 0.00186 AC XY: 323 AN XY: 173276

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.0000927

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000586

Gnomad4 FIN exome AF: 0.000391

Gnomad4 NFE exome AF: 0.00286

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00165 AC: 252 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.00146 AC XY: 109 AN XY: 74458

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00322

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00251 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Apr 05, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138219395; hg19: chr14-101302607;