Genetic Variant OLIG1:p.Gln231Pro (chr21-33070938-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_138983.3(OLIG1):c.692A>C(p.Gln231Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,455,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. Q231K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

OLIG1
NM_138983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14124241).

BS2

High AC in GnomAd4 at 22 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.692A>C	p.Gln231Pro	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.692A>C	p.Gln231Pro	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
ENSG00000227757	ENST00000454622.2	TSL:2	n.167T>G		non_coding_transcript_exon	Exon 1 of 2
ENSG00000227757	ENST00000777421.1		n.57T>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151730

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:

0.000309

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

67584

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.0000789

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000229

AC:

299

AN:

1303612

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

146

AN XY:

642308

show subpopulations

African (AFR)

AF:

0.0000770

AC:

AN:

25982

American (AMR)

AF:

0.0000427

AC:

AN:

23420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22416

East Asian (EAS)

AF:

0.00

AC:

AN:

27878

South Asian (SAS)

AF:

0.00

AC:

AN:

70882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3838

European-Non Finnish (NFE)

AF:

0.000269

AC:

281

AN:

1042916

Other (OTH)

AF:

0.000278

AC:

AN:

53880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000145

AC:

AN:

151836

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41496

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000174

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

0.068

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.11

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.14

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.77

REVEL

Benign

0.24

Sift

Benign

0.15

Sift4G

Benign

0.33

Polyphen

0.013

Vest4

0.26

MutPred

0.35

Gain of disorder (P = 0.0396)

MVP

0.83

MPC

1.7

ClinPred

0.029

GERP RS

3.5

PromoterAI

0.050

Neutral

(source)

Varity_R

0.21

gMVP

0.43

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over