6-29661106-C-G

Variant names:

• chr6-29661106-C-G
• rs2535260
• NM_206809.4:c.436+1440C>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.436+1440C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,116 control chromosomes in the GnomAD database, including 4,306 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 0.23 (4306 hom., cov: 32)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 18 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.436+1440C>G		intron_variant	Intron 2 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.436+1440C>G		intron_variant	Intron 2 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34322 AN: 151998 Hom.: 4302 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.226 AC: 34356 AN: 152116 Hom.: 4306 Cov.: 32 AF XY: 0.221 AC XY: 16453 AN XY: 74354

African (AFR) AF: 0.306 AC: 12684 AN: 41474

American (AMR) AF: 0.286 AC: 4375 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1220 AN: 3472

East Asian (EAS) AF: 0.0485 AC: 251 AN: 5174

South Asian (SAS) AF: 0.127 AC: 612 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13243 AN: 67990

Other (OTH) AF: 0.265 AC: 559 AN: 2110

Alfa AF: 0.180 Hom.: 1539

Bravo AF: 0.244

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.066
DANN	Benign	0.40
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: rs2535260; hg19: chr6-29628883;