Variant 6-29659536-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_206809.4(MOG):c.306A>G(p.Lys102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,613,114 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0087 ( 8 hom., cov: 31)

Exomes 𝑓: 0.013 ( 162 hom. )

Consequence

MOG
NM_206809.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0190

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 6-29659536-A-G is Benign according to our data. Variant chr6-29659536-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056332.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.019 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0129 (18796/1460778) while in subpopulation MID AF= 0.021 (121/5768). AF 95% confidence interval is 0.0179. There are 162 homozygotes in gnomad4_exome. There are 9352 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4 linkuse as main transcript	c.306A>G	p.Lys102=	synonymous_variant	2/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8 linkuse as main transcript	c.306A>G	p.Lys102=	synonymous_variant	2/8	1	NM_206809.4	P1	Q16653-1

Frequencies

GnomAD3 genomes

AF:

0.00873

AC:

1329

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00955

AC:

2356

AN:

246652

Hom.:

AF XY:

0.0102

AC XY:

1369

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00539

Gnomad ASJ exome

AF:

0.00431

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00570

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0129

AC:

18796

AN:

1460778

Hom.:

162

Cov.:

AF XY:

0.0129

AC XY:

9352

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.00552

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00871

AC:

1327

AN:

152336

Hom.:

Cov.:

AF XY:

0.00820

AC XY:

611

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00921

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.00921

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0199

EpiControl

AF:

0.0195

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MOG-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2020

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.2

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over