dbSNP rs894272792: OLIG1:p.Ser221Ala (chr21-33070907-T-G) – 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.661T>G(p.Ser221Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000916 in 1,418,554 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 (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

OLIG1
NM_138983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.488

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=0.20462623).

BS2

High AC in GnomAd4 at 7 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.661T>G	p.Ser221Ala	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.661T>G	p.Ser221Ala	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
ENSG00000227757	ENST00000454622.2	TSL:2	n.198A>C		non_coding_transcript_exon	Exon 1 of 2
ENSG00000227757	ENST00000777421.1		n.88A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000474

AC:

AN:

1267074

Hom.:

Cov.:

AF XY:

0.00000321

AC XY:

AN XY:

622684

show subpopulations

African (AFR)

AF:

0.000199

AC:

AN:

25086

American (AMR)

AF:

0.00

AC:

AN:

18764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20560

East Asian (EAS)

AF:

0.00

AC:

AN:

27254

South Asian (SAS)

AF:

0.00

AC:

AN:

65266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3694

European-Non Finnish (NFE)

AF:

9.77e-7

AC:

AN:

1023220

Other (OTH)

AF:

0.00

AC:

AN:

51938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000462

AC:

AN:

151480

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73968

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41344

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67844

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000142

Hom.:

Bravo

AF:

0.0000756

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

0.14

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.28

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

0.69

PhyloP100

0.49

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.73

REVEL

Benign

0.21

Sift

Benign

0.061

Sift4G

Benign

1.0

Polyphen

0.012

Vest4

0.11

MutPred

0.31

Gain of helix (P = 0.0128)

MVP

0.79

MPC

2.4

ClinPred

0.19

GERP RS

3.3

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.19

gMVP

0.24

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over