rs2857766

Positions:

• chr6-29666226-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_206809.4(MOG):​c.511G>C​(p.Val171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,610,262 control chromosomes in the GnomAD database, including 40,265 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3156 hom., cov: 31)
  • Exomes 𝑓: 0.22 (37109 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.303

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008852869).
• BP6: Variant 6-29666226-G-C is Benign according to our data. Variant chr6-29666226-G-C is described in ClinVar as [Benign]. Clinvar id is 3059372.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.511G>C	p.Val171Leu	missense_variant	3/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.511G>C	p.Val171Leu	missense_variant	3/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29517 AN: 151918 Hom.: 3155 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.222 AC: 54792 AN: 246528 Hom.: 6857 AF XY: 0.216 AC XY: 29005 AN XY: 134334

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.290

Gnomad SAS exome AF: 0.0998

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.220 AC: 320474 AN: 1458228 Hom.: 37109 Cov.: 32 AF XY: 0.217 AC XY: 157182 AN XY: 725530

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.194 AC: 29520 AN: 152034 Hom.: 3156 Cov.: 31 AF XY: 0.195 AC XY: 14464 AN XY: 74302

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.159

Alfa AF: 0.222 Hom.: 2973

Bravo AF: 0.186

TwinsUK AF: 0.232 AC: 861

ALSPAC AF: 0.242 AC: 934

ESP6500AA AF: 0.122 AC: 368

ESP6500EA AF: 0.228 AC: 1233

ExAC AF: 0.220 AC: 26034

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MOG-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.8
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.70	T;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0089	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;L;.;.;L;L;L;L;L
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.53	N;N;N;N;D;N;N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0040	B;B;.;B;B;.;.;B;B;P;B
Vest4		0.14
MPC		0.24
ClinPred		0.0040	T
GERP RS		0.63
Varity_R		0.054
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2857766; hg19: chr6-29634003;