14-100835270-GC-G

Variant names:

• chr14-100835270-GC-G
• rs370847475
• ENST00000398461.5:n.2309delC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000398461.5(MEG3):​n.2309delC 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 0.00739 in 158,932 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (0 hom.)
• Consequence: MEG3 ENST00000398461.5 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.218

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:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 14-100835270-GC-G is Benign according to our data. Variant chr14-100835270-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644541.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_002766.2	n.1050-890delC		intron_variant	Intron 4 of 6
MEG3	NR_003530.2	n.1299+526delC		intron_variant	Intron 6 of 8
MEG3	NR_003531.3	n.1026-462delC		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.5	n.2309delC		non_coding_transcript_exon_variant	Exon 1 of 4	1
MEG3	ENST00000429159.6	n.1066-890delC		intron_variant	Intron 4 of 6	1
MEG3	ENST00000451743.6	n.1032-890delC		intron_variant	Intron 4 of 6	1

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1148 AN: 152076 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00907

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00371 AC: 25 AN: 6736 Hom.: 0 Cov.: 0 AF XY: 0.00304 AC XY: 11 AN XY: 3622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00877

Gnomad4 NFE exome AF: 0.00466

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome AF: 0.00755 AC: 1149 AN: 152196 Hom.: 11 Cov.: 32 AF XY: 0.00906 AC XY: 674 AN XY: 74418

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.00907

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00517 Hom.: 2

Bravo AF: 0.00518

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

MEG3: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs370847475; hg19: chr14-101301607;