6-29661567-T-C

Variant names:

• chr6-29661567-T-C
• rs3130251
• NM_206809.4:c.436+1901T>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.436+1901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 983,712 control chromosomes in the GnomAD database, including 24,212 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 0.17 (2522 hom., cov: 31)
  • Exomes 𝑓: 0.23 (21690 hom.)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 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.436+1901T>C		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.436+1901T>C		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.436+1901T>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.436+1901T>C		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.436+1901T>C		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.436+1901T>C		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25227 AN: 151862 Hom.: 2510 Cov.: 31

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.226 AC: 187981 AN: 831732 Hom.: 21690 Cov.: 23 AF XY: 0.226 AC XY: 86913 AN XY: 384118

African (AFR) AF: 0.0558 AC: 880 AN: 15758

American (AMR) AF: 0.259 AC: 254 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 847 AN: 5144

East Asian (EAS) AF: 0.323 AC: 1170 AN: 3626

South Asian (SAS) AF: 0.313 AC: 5146 AN: 16444

European-Finnish (FIN) AF: 0.127 AC: 35 AN: 276

Middle Eastern (MID) AF: 0.159 AC: 258 AN: 1620

European-Non Finnish (NFE) AF: 0.227 AC: 172719 AN: 760638

Other (OTH) AF: 0.245 AC: 6672 AN: 27244

GnomAD4 genome AF: 0.166 AC: 25254 AN: 151980 Hom.: 2522 Cov.: 31 AF XY: 0.166 AC XY: 12311 AN XY: 74278

African (AFR) AF: 0.0677 AC: 2808 AN: 41460

American (AMR) AF: 0.181 AC: 2763 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1675 AN: 5152

South Asian (SAS) AF: 0.311 AC: 1502 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1326 AN: 10542

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14023 AN: 67970

Other (OTH) AF: 0.168 AC: 353 AN: 2104

Alfa AF: 0.0841 Hom.: 130

Bravo AF: 0.161

Asia WGS AF: 0.384 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.65
PhyloP100		0.58
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: rs3130251; hg19: chr6-29629344;