rs2400963

Positions:

• chr14-100929369-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.1043-6403A>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 0.175 in 152,160 control chromosomes in the GnomAD database, including 3,122 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 0.18 (3122 hom., cov: 32)
• Consequence: MEG8 NR_146000.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEG8	NR_146000.1	n.1043-6403A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEG8	ENST00000638012.2	n.687-6403A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26696 AN: 152042 Hom.: 3124 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.175 AC: 26684 AN: 152160 Hom.: 3122 Cov.: 32 AF XY: 0.169 AC XY: 12603 AN XY: 74402

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.221

Alfa AF: 0.250 Hom.: 10464

Bravo AF: 0.174

Asia WGS AF: 0.108 AC: 378 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	1.4
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2400963; hg19: chr14-101395706;