14-100829493-G-C

Position:

• chr14-100829493-G-C

Variant summary

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

The ENST00000429159.6(MEG3):​n.679G>C 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 0.936 in 152,330 control chromosomes in the GnomAD database, including 66,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.94 (66758 hom., cov: 33)
  • Exomes 𝑓: 0.96 (23 hom.)
• Consequence: MEG3 ENST00000429159.6 non_coding_transcript_exon
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.50

Genes affected

MEG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 14-100829493-G-C is Benign according to our data. Variant chr14-100829493-G-C is described in ClinVar as [Benign]. Clinvar id is 3059566.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEG3	NR_002766.2	n.679G>C		non_coding_transcript_exon_variant	3/7
MEG3	NR_003530.2	n.679G>C		non_coding_transcript_exon_variant	3/9
MEG3	NR_003531.3	n.655G>C		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000429159.6	n.679G>C		non_coding_transcript_exon_variant	3/7	1
MEG3	ENST00000451743.6	n.661G>C		non_coding_transcript_exon_variant	3/7	1
MEG3	ENST00000521404.5	n.661G>C		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142460 AN: 152162 Hom.: 66706 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.939

GnomAD4 exome AF: 0.960 AC: 48 AN: 50 Hom.: 23 Cov.: 0 AF XY: 1.00 AC XY: 26 AN XY: 26

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.936 AC: 142570 AN: 152280 Hom.: 66758 Cov.: 33 AF XY: 0.938 AC XY: 69815 AN XY: 74462

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.978

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.939

Alfa AF: 0.928 Hom.: 7629

Bravo AF: 0.936

Asia WGS AF: 0.979 AC: 3400 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEG3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

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	-0.99
CADD	Benign	0.56
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs941575; hg19: chr14-101295830;