6-29657761-A-G

Variant names:

• chr6-29657761-A-G
• rs2262263
• NM_206809.4:c.88+464A>G

Variant summary

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

The NM_206809.4(MOG):​c.88+464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 147,152 control chromosomes in the GnomAD database, including 5,762 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 0.27 (5762 hom., cov: 28)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 3 publications found

Genes affected

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MOG Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.88+464A>G		intron_variant	Intron 1 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.88+464A>G		intron_variant	Intron 1 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 39620 AN: 147052 Hom.: 5757 Cov.: 28

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.270 AC: 39660 AN: 147152 Hom.: 5762 Cov.: 28 AF XY: 0.266 AC XY: 18928 AN XY: 71222

African (AFR) AF: 0.347 AC: 13757 AN: 39612

American (AMR) AF: 0.374 AC: 5410 AN: 14458

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1398 AN: 3460

East Asian (EAS) AF: 0.0573 AC: 285 AN: 4974

South Asian (SAS) AF: 0.168 AC: 790 AN: 4716

European-Finnish (FIN) AF: 0.143 AC: 1318 AN: 9224

Middle Eastern (MID) AF: 0.304 AC: 82 AN: 270

European-Non Finnish (NFE) AF: 0.235 AC: 15832 AN: 67464

Other (OTH) AF: 0.315 AC: 650 AN: 2064

Alfa AF: 0.238 Hom.: 605

Bravo AF: 0.287

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
DANN	Benign	0.15
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2262263; hg19: chr6-29625538;