ENST00000398461.5:n.3121+3611A>C

Variant names:

• chr14-100849144-A-C
• rs4900478
• ENST00000398461.5:n.3121+3611A>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000398461.5(MEG3):​n.3121+3611A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,104 control chromosomes in the GnomAD database, including 6,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (6169 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: MEG3 ENST00000398461.5 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.315

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-100849144-A-C is Benign according to our data. Variant chr14-100849144-A-C is described in ClinVar as [Benign]. Clinvar id is 3056978.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_046473.1	n.4528A>C		non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1	n.4638A>C		non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1	n.4768A>C		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+3611A>C		intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.6	n.1275+3611A>C		intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.6	n.1241+3611A>C		intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40240 AN: 151982 Hom.: 6177 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 40234 AN: 152100 Hom.: 6169 Cov.: 32 AF XY: 0.266 AC XY: 19798 AN XY: 74340

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.252

Alfa AF: 0.316 Hom.: 2445

Bravo AF: 0.256

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Nov 01, 2019

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4900478; hg19: chr14-101315481;