rs10145110

Positions:

• chr14-101008533-C-T

Variant summary

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

The XM_047432049.1(LOC124903407):​c.368-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 152,226 control chromosomes in the GnomAD database, including 1,154 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 0.095 (1154 hom., cov: 32)
• Consequence: LOC124903407 XM_047432049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

Genes affected

LOC124903407 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903407	XM_047432049.1	c.368-146C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEG8	ENST00000636391.2	n.1985-1025C>T		intron_variant, non_coding_transcript_variant		5
MEG8	ENST00000668545.1	n.83+65C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14386 AN: 152108 Hom.: 1145 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0697

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0948 AC: 14435 AN: 152226 Hom.: 1154 Cov.: 32 AF XY: 0.0920 AC XY: 6850 AN XY: 74456

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0419

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.0541 Hom.: 318

Bravo AF: 0.105

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10145110; hg19: chr14-101474870;