rs2400963

Variant names:

• chr14-100929369-A-G
• rs2400963
• ENST00000556475.1:n.253-6403A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556475.1(MEG8):​n.253-6403A>G variant causes a intron 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 ENST00000556475.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 14 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]

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

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 (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEG8	NR_146000.1	n.1043-6403A>G		intron_variant	Intron 9 of 50

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEG8	ENST00000556475.1	n.253-6403A>G		intron_variant	Intron 3 of 3	3
MEG8	ENST00000636052.2	n.771-6403A>G		intron_variant	Intron 7 of 24	5
MIR493HG	ENST00000637474.1	n.1151-6403A>G		intron_variant	Intron 11 of 18	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

African (AFR) AF: 0.0516 AC: 2145 AN: 41542

American (AMR) AF: 0.169 AC: 2577 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.0515 AC: 267 AN: 5180

South Asian (SAS) AF: 0.116 AC: 559 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10592

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17691 AN: 67952

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.236 Hom.: 15031

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
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs2400963; hg19: chr14-101395706;