rs11080149

Positions:

• chr17-31296270-C-T

Variant summary

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

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. 15/20 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 0.081 (686 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11389 hom.)
• Consequence: OMG NM_002544.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.45

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]

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]

OMG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
OMG	NM_002544.5	c.62G>A	p.Gly21Asp	missense_variant	2/2	ENST00000247271.5	NP_002535.3
NF1	NM_001042492.3	c.4836-29550C>T		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-29550C>T		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OMG	ENST00000247271.5	c.62G>A	p.Gly21Asp	missense_variant	2/2	1	NM_002544.5	ENSP00000247271.4
NF1	ENST00000358273.9	c.4836-29550C>T		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12354 AN: 152084 Hom.: 686 Cov.: 32

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

GnomAD3 exomes AF: 0.0912 AC: 22893 AN: 251078 Hom.: 1328 AF XY: 0.0909 AC XY: 12336 AN XY: 135738

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 SAS exome AF: 0.0431

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.: 32 AF XY: 0.115 AC XY: 83976 AN XY: 727156

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.0811

Gnomad4 ASJ exome AF: 0.0676

Gnomad4 EAS exome AF: 0.000630

Gnomad4 SAS exome AF: 0.0428

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.0989

GnomAD4 genome AF: 0.0812 AC: 12352 AN: 152202 Hom.: 686 Cov.: 32 AF XY: 0.0803 AC XY: 5974 AN XY: 74410

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0766

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0415

Gnomad4 FIN AF: 0.0943

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.112 Hom.: 2668

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: 61 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

OMG-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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	0.16
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.085
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.42	T
Polyphen		0.019	B
Vest4		0.14
MPC		0.89
ClinPred		0.021	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs11080149; hg19: chr17-29623288; COSMIC: COSV55988007;