rs2535262

Positions:

• chr6-29660456-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206809.4(MOG):​c.436+790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 148,110 control chromosomes in the GnomAD database, including 2,479 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 (2479 hom., cov: 24)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOG	NM_206809.4	c.436+790G>A		intron_variant		ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.436+790G>A		intron_variant		1	NM_206809.4	ENSP00000366115	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 25554 AN: 148000 Hom.: 2476 Cov.: 24

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.173 AC: 25577 AN: 148110 Hom.: 2479 Cov.: 24 AF XY: 0.170 AC XY: 12228 AN XY: 71992

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.203

Alfa AF: 0.173 Hom.: 299

Bravo AF: 0.184

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2535262; hg19: chr6-29628233;