rs941576

Variant names:

• chr14-100839708-A-G
• rs941576
• ENST00000398461.6:n.3045+3408A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-100839708-A-G
• chr14-100839708-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398461.6(MEG3):​n.3045+3408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,982 control chromosomes in the GnomAD database, including 15,283 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 0.44 (15283 hom., cov: 32)
• Consequence: MEG3 ENST00000398461.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 59 publications found

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:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG3	NR_002766.2	n.1183+3408A>G		intron_variant	Intron 5 of 6
MEG3	NR_003530.2	n.1433+3408A>G		intron_variant	Intron 7 of 8
MEG3	NR_003531.3	n.1300+3408A>G		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG3	ENST00000398461.6	n.3045+3408A>G		intron_variant	Intron 2 of 3	1
MEG3	ENST00000429159.7	n.1199+3408A>G		intron_variant	Intron 5 of 6	1
MEG3	ENST00000451743.7	n.1183+3408A>G		intron_variant	Intron 5 of 6	1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67564 AN: 151864 Hom.: 15278 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67613 AN: 151982 Hom.: 15283 Cov.: 32 AF XY: 0.443 AC XY: 32927 AN XY: 74258

African (AFR) AF: 0.449 AC: 18603 AN: 41478

American (AMR) AF: 0.467 AC: 7131 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3464

East Asian (EAS) AF: 0.314 AC: 1611 AN: 5124

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5517 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30432 AN: 67924

Other (OTH) AF: 0.442 AC: 933 AN: 2110

Alfa AF: 0.437 Hom.: 6095

Bravo AF: 0.446

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		0.76

Splicing

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

Other links and lift over

dbSNP: rs941576; hg19: chr14-101306045;