Genetic Variant OLIG1:p.Arg95Trp (chr21-33070529-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_138983.3(OLIG1):c.283C>T(p.Arg95Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000034 in 1,499,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

OLIG1
NM_138983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.129

Publications

0 publications found

Variant links:

Genes affected

OLIG1 (HGNC:16983): (oligodendrocyte transcription factor 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in neuron differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within neuron fate commitment. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OLIG1 links:

ENSG00000227757 (HGNC:):

ENSG00000227757 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 49 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLIG1	NM_138983.3	MANE Select	c.283C>T	p.Arg95Trp	missense	Exon 1 of 1	NP_620450.2	Q8TAK6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OLIG1	ENST00000382348.2	TSL:6 MANE Select	c.283C>T	p.Arg95Trp	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
ENSG00000227757	ENST00000454622.2	TSL:2	n.201+375G>A		intron	N/A
ENSG00000227757	ENST00000777421.1		n.91+375G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

97058

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1348032

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

664882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27302

American (AMR)

AF:

0.00

AC:

AN:

30196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23636

East Asian (EAS)

AF:

0.00

AC:

AN:

30884

South Asian (SAS)

AF:

0.00

AC:

AN:

74974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4798

European-Non Finnish (NFE)

AF:

0.0000433

AC:

AN:

1062488

Other (OTH)

AF:

0.0000536

AC:

AN:

55992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67952

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.99

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.73

MutationAssessor

Benign

0.81

PhyloP100

-0.13

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.15

MutPred

0.21

Loss of helix (P = 0.0444)

MVP

0.95

MPC

2.4

ClinPred

0.76

GERP RS

1.1

PromoterAI

0.13

Neutral

(source)

Varity_R

0.26

gMVP

0.85

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over