14-100907636-A-G

Position:

• chr14-100907636-A-G

Variant summary

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

The NR_146000.1(MEG8):​n.880+504A>G 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 0.845 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 NR_146000.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MEG8	NR_146000.1	n.880+504A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEG8	ENST00000638012.2	n.524+504A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.799

Alfa AF: 0.810 Hom.: 6266

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1950626; hg19: chr14-101373973;