rs11080149

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002544.5(OMG):c.62G>A(p.Gly21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,850 control chromosomes in the GnomAD database, including 12,075 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.081 ( 686 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11389 hom. )

Consequence

OMG
NM_002544.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.45

Publications

43 publications found

Variant links:

Genes affected

OMG (HGNC:8135): (oligodendrocyte myelin glycoprotein) Predicted to enable identical protein binding activity. Predicted to be involved in neuron projection regeneration. Predicted to act upstream of or within regulation of collateral sprouting of intact axon in response to injury. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OMG links:

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 Gene-Disease associations (from GenCC):

neurofibromatosis type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Moyamoya disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014791489).

BP6

Variant 17-31296270-C-T is Benign according to our data. Variant chr17-31296270-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055468.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OMG	NM_002544.5 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 2 of 2	ENST00000247271.5	NP_002535.3	P23515
NF1	NM_001042492.3 link	c.4836-29550C>T		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.4 link	c.4773-29550C>T		intron_variant	Intron 35 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OMG	ENST00000247271.5 link	c.62G>A	p.Gly21Asp	missense_variant	Exon 2 of 2	1	NM_002544.5	ENSP00000247271.4		P23515
NF1	ENST00000358273.9 link	c.4836-29550C>T		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

12354

AN:

152084

Hom.:

686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0767

Gnomad ASJ

AF:

0.0655

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.0943

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0708

GnomAD2 exomes

AF:

0.0912

AC:

22893

AN:

251078

AF XY:

0.0909

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.0821

Gnomad ASJ exome

AF:

0.0660

Gnomad EAS exome

AF:

0.000925

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.0875

GnomAD4 exome

AF:

0.118

AC:

172364

AN:

1461648

Hom.:

11389

Cov.:

AF XY:

0.115

AC XY:

83976

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0207

AC:

694

AN:

33474

American (AMR)

AF:

0.0811

AC:

3628

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0676

AC:

1767

AN:

26132

East Asian (EAS)

AF:

0.000630

AC:

AN:

39692

South Asian (SAS)

AF:

0.0428

AC:

3691

AN:

86252

European-Finnish (FIN)

AF:

0.105

AC:

5623

AN:

53414

Middle Eastern (MID)

AF:

0.0392

AC:

226

AN:

5768

European-Non Finnish (NFE)

AF:

0.136

AC:

150739

AN:

1111812

Other (OTH)

AF:

0.0989

AC:

5971

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

7978

15956

23933

31911

39889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5278

10556

15834

21112

26390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0812

AC:

12352

AN:

152202

Hom.:

686

Cov.:

AF XY:

0.0803

AC XY:

5974

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0245

AC:

1020

AN:

41548

American (AMR)

AF:

0.0766

AC:

1171

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0655

AC:

227

AN:

3466

East Asian (EAS)

AF:

0.000578

AC:

AN:

5192

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4824

European-Finnish (FIN)

AF:

0.0943

AC:

998

AN:

10584

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8488

AN:

67992

Other (OTH)

AF:

0.0696

AC:

147

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

574

1149

1723

2298

2872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.107

Hom.:

3405

Bravo

AF:

0.0775

TwinsUK

AF:

0.139

AC:

516

ALSPAC

AF:

0.135

AC:

520

ESP6500AA

AF:

0.0256

AC:

113

ESP6500EA

AF:

0.120

AC:

1032

ExAC

AF:

0.0926

AC:

11246

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OMG-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.063

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.69

REVEL

Benign

0.035

Sift

Uncertain

0.0030

Sift4G

Benign

0.42

Polyphen

0.019

Vest4

0.14

MPC

0.89

ClinPred

0.021

GERP RS

3.1

Varity_R

0.14

gMVP

0.37

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over