6-29659172-C-G

Variant names:

• chr6-29659172-C-G
• rs16895223
• NM_206809.4:c.89-147C>G

Variant summary

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

The ENST00000376917.8(MOG):​c.89-147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 719,312 control chromosomes in the GnomAD database, including 9,107 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 (3042 hom., cov: 31)
  • Exomes 𝑓: 0.14 (6065 hom.)
• Consequence: MOG ENST00000376917.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 4 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376917.8. 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.89-147C>G		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.89-147C>G		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.89-147C>G		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.89-147C>G		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.89-147C>G		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.89-147C>G		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28051 AN: 151830 Hom.: 3039 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.140 AC: 79348 AN: 567364 Hom.: 6065 AF XY: 0.142 AC XY: 43324 AN XY: 304134

African (AFR) AF: 0.307 AC: 4595 AN: 14954

American (AMR) AF: 0.114 AC: 3298 AN: 28956

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 2569 AN: 16294

East Asian (EAS) AF: 0.105 AC: 3690 AN: 35248

South Asian (SAS) AF: 0.175 AC: 9874 AN: 56532

European-Finnish (FIN) AF: 0.116 AC: 5119 AN: 44300

Middle Eastern (MID) AF: 0.199 AC: 436 AN: 2192

European-Non Finnish (NFE) AF: 0.133 AC: 45201 AN: 338614

Other (OTH) AF: 0.151 AC: 4566 AN: 30274

GnomAD4 genome AF: 0.185 AC: 28079 AN: 151948 Hom.: 3042 Cov.: 31 AF XY: 0.185 AC XY: 13729 AN XY: 74292

African (AFR) AF: 0.302 AC: 12484 AN: 41404

American (AMR) AF: 0.146 AC: 2230 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3466

East Asian (EAS) AF: 0.191 AC: 989 AN: 5172

South Asian (SAS) AF: 0.172 AC: 829 AN: 4810

European-Finnish (FIN) AF: 0.110 AC: 1163 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9273 AN: 67928

Other (OTH) AF: 0.185 AC: 391 AN: 2114

Alfa AF: 0.0691 Hom.: 81

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.053
DANN	Benign	0.31
PhyloP100		-2.2
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: rs16895223; hg19: chr6-29626949;