rs2071653

Variant names:

• chr6-29668151-T-C
• rs2071653
• NM_206809.4:c.592+227T>C

Variant summary

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

The NM_206809.4(MOG):​c.592+227T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,178 control chromosomes in the GnomAD database, including 48,389 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 0.80 (48389 hom., cov: 33)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 34 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.592+227T>C		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.592+227T>C		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.592+227T>C		intron	N/A	NP_002424.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.592+227T>C		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.592+227T>C		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.592+227T>C		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120947 AN: 152060 Hom.: 48343 Cov.: 33

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.795 AC: 121052 AN: 152178 Hom.: 48389 Cov.: 33 AF XY: 0.791 AC XY: 58857 AN XY: 74404

African (AFR) AF: 0.811 AC: 33668 AN: 41506

American (AMR) AF: 0.849 AC: 12983 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2849 AN: 3468

East Asian (EAS) AF: 0.849 AC: 4401 AN: 5182

South Asian (SAS) AF: 0.765 AC: 3691 AN: 4824

European-Finnish (FIN) AF: 0.656 AC: 6939 AN: 10584

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.792 AC: 53890 AN: 68006

Other (OTH) AF: 0.801 AC: 1691 AN: 2110

Alfa AF: 0.798 Hom.: 188266

Bravo AF: 0.813

Asia WGS AF: 0.829 AC: 2885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.57
PhyloP100		-0.76
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: rs2071653; hg19: chr6-29635928;