14-100907636-A-C

Variant names:

• chr14-100907636-A-C
• rs1950626
• ENST00000553465.5:n.497+504A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000556475.1(MEG8):​n.90+504A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: MEG8 ENST00000556475.1 intron
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG8	ENST00000553465.5	n.497+504A>C		intron_variant	Intron 4 of 6	5
MEG8	ENST00000556475.1	n.90+504A>C		intron_variant	Intron 1 of 3	3
MEG8	ENST00000636052.1	n.608+504A>C		intron_variant	Intron 5 of 13	5

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
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;