Genetic Variant MEG3:n.1307C>T (chr14-100835753-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000398461.6(MEG3):n.2785C>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 0.171 in 174,500 control chromosomes in the GnomAD database, including 2,786 homozygotes. 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: 𝑓 0.18 ( 2501 hom., cov: 32)

Exomes 𝑓: 0.14 ( 285 hom. )

Consequence

MEG3
ENST00000398461.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.31

Publications

9 publications found

Variant links:

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]

MEG3 links:

ENSG00000258663 (HGNC:):

ENSG00000258663 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398461.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MEG3	NR_190993.1	MANE Select	n.1307C>T	non_coding_transcript_exon	Exon 7 of 10
MEG3	NR_003531.3		n.1040C>T	non_coding_transcript_exon	Exon 5 of 8
MEG3	NR_033359.1		n.1032C>T	non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MEG3	ENST00000649261.2	MANE Select	n.1307C>T	non_coding_transcript_exon	Exon 7 of 10
MEG3	ENST00000398461.6	TSL:1	n.2785C>T	non_coding_transcript_exon	Exon 1 of 4
MEG3	ENST00000554639.6	TSL:1	n.1054C>T	non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26691

AN:

152088

Hom.:

2502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.144

AC:

3205

AN:

22294

Hom.:

285

Cov.:

AF XY:

0.139

AC XY:

1607

AN XY:

11592

show subpopulations

African (AFR)

AF:

0.201

AC:

AN:

134

American (AMR)

AF:

0.117

AC:

AN:

358

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

AN:

458

East Asian (EAS)

AF:

0.00

AC:

AN:

182

South Asian (SAS)

AF:

0.116

AC:

241

AN:

2074

European-Finnish (FIN)

AF:

0.122

AC:

153

AN:

1258

Middle Eastern (MID)

AF:

0.245

AC:

AN:

European-Non Finnish (NFE)

AF:

0.150

AC:

2447

AN:

16294

Other (OTH)

AF:

0.143

AC:

205

AN:

1438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

132

264

395

527

659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.175

AC:

26693

AN:

152206

Hom.:

2501

Cov.:

AF XY:

0.171

AC XY:

12723

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.225

AC:

9335

AN:

41526

American (AMR)

AF:

0.137

AC:

2091

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

546

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5170

South Asian (SAS)

AF:

0.126

AC:

607

AN:

4826

European-Finnish (FIN)

AF:

0.137

AC:

1454

AN:

10616

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12105

AN:

67982

Other (OTH)

AF:

0.179

AC:

378

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1138

2276

3414

4552

5690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

471

Bravo

AF:

0.178

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.073

(source)

DANN

Benign

0.58

PhyloP100

-4.3

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over