dbSNP rs1054013: MEG3:n.3121+999G>A (chr14-100846532-G-A) – 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.3121+999G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,262 control chromosomes in the GnomAD database, including 5,943 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 0.26 ( 5942 hom., cov: 33)

Exomes 𝑓: 0.28 ( 1 hom. )

Consequence

MEG3
ENST00000398461.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.288

Publications

14 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:

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

MIR493HG links:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MEG3	NR_046473.1 link	n.1916G>A	non_coding_transcript_exon_variant	Exon 7 of 7
MEG3	NR_190994.1 link	n.2026G>A	non_coding_transcript_exon_variant	Exon 8 of 8
MEG3	NR_190995.1 link	n.2156G>A	non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MEG3	ENST00000398461.6 link	n.3121+999G>A	intron_variant	Intron 3 of 3	1
MEG3	ENST00000429159.7 link	n.1275+999G>A	intron_variant	Intron 6 of 6	1
MEG3	ENST00000451743.7 link	n.1259+999G>A	intron_variant	Intron 6 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39140

AN:

152098

Hom.:

5951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0885

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.283

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.350

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

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:

0.257

AC:

39124

AN:

152216

Hom.:

5942

Cov.:

AF XY:

0.259

AC XY:

19288

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0884

AC:

3673

AN:

41560

American (AMR)

AF:

0.309

AC:

4730

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1155

AN:

3466

East Asian (EAS)

AF:

0.266

AC:

1377

AN:

5182

South Asian (SAS)

AF:

0.289

AC:

1393

AN:

4816

European-Finnish (FIN)

AF:

0.329

AC:

3484

AN:

10582

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.328

AC:

22317

AN:

68002

Other (OTH)

AF:

0.247

AC:

523

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1448

2897

4345

5794

7242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.302

Hom.:

20467

Bravo

AF:

0.248

Asia WGS

AF:

0.243

AC:

844

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.9

(source)

DANN

Benign

0.49

PhyloP100

0.29

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over