rs12590815

Variant names:

• chr14-101037672-C-T
• rs12590815
• ENST00000636391.2:n.2503+29C>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 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
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG8	ENST00000636391.2	n.2503+29C>T		intron_variant	Intron 28 of 28	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;