Variant 21-33070938-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

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

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG1	NM_138983.3 linkuse as main transcript	c.692A>C	p.Gln231Pro	missense_variant	1/1	ENST00000382348.2	NP_620450.2	Q8TAK6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OLIG1	ENST00000382348.2 linkuse as main transcript	c.692A>C	p.Gln231Pro	missense_variant	1/1	6	NM_138983.3	ENSP00000371785.1	Q8TAK6
ENSG00000227757	ENST00000454622.2 linkuse as main transcript	n.167T>G		non_coding_transcript_exon_variant	1/2	2
OLIG1	ENST00000426947.5 linkuse as main transcript	c.-29A>C		upstream_gene_variant		2		ENSP00000414840.1	H7C404

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

GnomAD3 exomes

AF:

0.000104

AC:

AN:

67584

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

39540

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000770

Gnomad4 AMR exome

AF:

0.0000427

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.000278

GnomAD4 genome

AF:

0.000145

AC:

AN:

151836

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.692A>C (p.Q231P) alteration is located in exon 1 (coding exon 1) of the OLIG1 gene. This alteration results from a A to C substitution at nucleotide position 692, causing the glutamine (Q) at amino acid position 231 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.11

CADD

Benign

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

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

Varity_R

0.21

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over