ENST00000553465.6:n.497+504A>G

Variant names:

• chr14-100907636-A-G
• rs1950626
• ENST00000553465.6:n.497+504A>G

Variant summary

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

The ENST00000553465.6(MEG8):​n.497+504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,298 control chromosomes in the GnomAD database, including 54,982 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 0.84 (54982 hom., cov: 33)
• Consequence: MEG8 ENST00000553465.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 4 publications found

Genes affected

MEG8 (HGNC:14574): (maternally expressed 8, small nucleolar RNA host gene) This gene is located in a cluster of imprinted genes on chromosome 14q32.3. It encodes a a non-protein coding transcript that is preferentially expressed from the maternal allele in skeletal muscle, and appears to be coordinately regulated with other imprinted genes in this region. [provided by RefSeq, Oct 2010]

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG8	NR_146000.1	n.880+504A>G		intron_variant	Intron 7 of 50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG8	ENST00000553465.6	n.497+504A>G		intron_variant	Intron 4 of 6	5
MEG8	ENST00000553584.6	n.662+504A>G		intron_variant	Intron 4 of 5	3
MEG8	ENST00000556475.1	n.90+504A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128522 AN: 152180 Hom.: 54916 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.845 AC: 128648 AN: 152298 Hom.: 54982 Cov.: 33 AF XY: 0.850 AC XY: 63322 AN XY: 74454

African (AFR) AF: 0.954 AC: 39674 AN: 41568

American (AMR) AF: 0.846 AC: 12942 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2316 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5156 AN: 5184

South Asian (SAS) AF: 0.899 AC: 4336 AN: 4822

European-Finnish (FIN) AF: 0.873 AC: 9263 AN: 10606

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52269 AN: 68020

Other (OTH) AF: 0.799 AC: 1689 AN: 2114

Alfa AF: 0.815 Hom.: 6608

Bravo AF: 0.844

Asia WGS AF: 0.929 AC: 3230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.38
PhyloP100		0.70

Splicing

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

Other links and lift over

dbSNP: rs1950626; hg19: chr14-101373973;