rs12590815

chr14-101037672-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636391.2(MEG8):n.2503+29C>T 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 0.499 in 152,088 control chromosomes in the GnomAD database, including 20,207 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 0.50 (20198 hom., cov: 33)
  • Exomes 𝑓: 0.41 (9 hom.)
• Consequence: MEG8 ENST00000636391.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEG8	ENST00000636391.2	n.2503+29C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75855 AN: 151902 Hom.: 20170 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.409 AC: 27 AN: 66 Hom.: 9 Cov.: 0 AF XY: 0.364 AC XY: 16 AN XY: 44

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.500 AC: 75937 AN: 152022 Hom.: 20198 Cov.: 33 AF XY: 0.506 AC XY: 37567 AN XY: 74294

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.500

Alfa AF: 0.453 Hom.: 4402

Bravo AF: 0.513

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.6
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12590815; hg19: chr14-101504009;