Variant 21-33070391-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138983.3(OLIG1):c.145A>T(p.Thr49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000607 in 1,482,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

OLIG1
NM_138983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056554228).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OLIG1	NM_138983.3 linkuse as main transcript	c.145A>T	p.Thr49Ser	missense_variant	1/1	ENST00000382348.2	NP_620450.2	Q8TAK6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OLIG1	ENST00000382348.2 linkuse as main transcript	c.145A>T	p.Thr49Ser	missense_variant	1/1	6	NM_138983.3	ENSP00000371785.1		Q8TAK6
ENSG00000227757	ENST00000454622.2 linkuse as main transcript	n.201+513T>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000213

AC:

AN:

140576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000539

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:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000430

AC:

AN:

116166

Hom.:

AF XY:

0.0000640

AC XY:

AN XY:

62500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000433

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:

0.0000974

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000447

AC:

AN:

1341454

Hom.:

Cov.:

AF XY:

0.00000605

AC XY:

AN XY:

661306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000480

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000213

AC:

AN:

140670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68432

show subpopulations

Gnomad4 AFR

AF:

0.0000538

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:

0.0000157

Gnomad4 OTH

AF:

0.00

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

Sep 17, 2021

The c.145A>T (p.T49S) alteration is located in exon 1 (coding exon 1) of the OLIG1 gene. This alteration results from a A to T substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 to be replaced by a serine (S). 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

0.057

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

1.1

DANN

Benign

0.71

DEOGEN2

Benign

0.12

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.17

M_CAP

Benign

0.058

MetaRNN

Benign

0.057

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.65

REVEL

Benign

0.23

Sift

Benign

1.0

Sift4G

Benign

0.89

Polyphen

0.46

Vest4

0.13

MutPred

0.30

Loss of relative solvent accessibility (P = 0.0306);

MVP

0.49

MPC

1.7

ClinPred

0.071

GERP RS

-4.3

Varity_R

0.044

gMVP

0.20

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