14-100848826-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NR_046467.1(MEG3):​n.1427+3293A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,098 control chromosomes in the GnomAD database, including 6,175 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 ( 6174 hom., cov: 32)
Exomes 𝑓: 0.42 ( 1 hom. )

Consequence

MEG3
NR_046467.1 intron, non_coding_transcript

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.176
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 14-100848826-A-G is Benign according to our data. Variant chr14-100848826-A-G is described in ClinVar as [Benign]. Clinvar id is 3056329.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/exons MANE Protein UniProt
MEG3NR_046467.1 linkuse as main transcriptn.1427+3293A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENST00000554041.1 linkuse as main transcriptn.143+12058T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.265
AC:
40246
AN:
151970
Hom.:
6182
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.435
Gnomad AMR
AF:
0.314
Gnomad ASJ
AF:
0.334
Gnomad EAS
AF:
0.267
Gnomad SAS
AF:
0.291
Gnomad FIN
AF:
0.331
Gnomad MID
AF:
0.271
Gnomad NFE
AF:
0.335
Gnomad OTH
AF:
0.256
GnomAD4 exome
AF:
0.417
AC:
5
AN:
12
Hom.:
1
Cov.:
0
AF XY:
0.500
AC XY:
1
AN XY:
2
show subpopulations
Gnomad4 FIN exome
AF:
0.400
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.265
AC:
40239
AN:
152086
Hom.:
6174
Cov.:
32
AF XY:
0.267
AC XY:
19813
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.314
Gnomad4 ASJ
AF:
0.334
Gnomad4 EAS
AF:
0.266
Gnomad4 SAS
AF:
0.292
Gnomad4 FIN
AF:
0.331
Gnomad4 NFE
AF:
0.335
Gnomad4 OTH
AF:
0.252
Alfa
AF:
0.320
Hom.:
2837
Bravo
AF:
0.255
Asia WGS
AF:
0.249
AC:
866
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MEG3-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 19, 2019This 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
-0.85
CADD
Benign
0.38
DANN
Benign
0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7155428; hg19: chr14-101315163; API