rs12590815

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.833 AC: 5 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.452 AC: 19 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.636 AC: 26389 AN: 41468

American (AMR) AF: 0.571 AC: 8726 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1601 AN: 3470

East Asian (EAS) AF: 0.764 AC: 3940 AN: 5154

South Asian (SAS) AF: 0.566 AC: 2729 AN: 4822

European-Finnish (FIN) AF: 0.420 AC: 4429 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26512 AN: 67968

Other (OTH) AF: 0.500 AC: 1059 AN: 2116

Alfa AF: 0.447 Hom.: 8386

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
PhyloP100		-0.0060

Splicing

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

Other links and lift over

dbSNP: rs12590815; hg19: chr14-101504009;