Genetic Variant OLIG1:p.Gln231Arg (chr21-33070938-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138983.3(OLIG1):c.692A>G(p.Gln231Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q231P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

OLIG1
NM_138983.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24477848).

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>G	p.Gln231Arg	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>G	p.Gln231Arg	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
ENSG00000227757	ENST00000454622.2	TSL:2	n.167T>C		non_coding_transcript_exon	Exon 1 of 2
ENSG00000227757	ENST00000777421.1		n.57T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.67e-7

AC:

AN:

1303616

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25982

American (AMR)

AF:

0.00

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:

9.59e-7

AC:

AN:

1042918

Other (OTH)

AF:

0.00

AC:

AN:

53882

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

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.24

MetaSVM

Uncertain

0.091

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.57

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Benign

0.42

Polyphen

0.053

Vest4

0.14

MutPred

0.37

Gain of methylation at Q231 (P = 0.021)

MVP

0.79

MPC

2.0

ClinPred

0.13

GERP RS

3.5

PromoterAI

0.020

Neutral

(source)

Varity_R

0.16

gMVP

0.40

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over