rs1170507348

Variant names:

• chr21-33070529-C-G
• rs1170507348
• NM_138983.3:c.283C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-33070529-C-G
• chr21-33070529-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_138983.3(OLIG1):​c.283C>G​(p.Arg95Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 1,499,984 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. R95W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: OLIG1 NM_138983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.129
• Publications: 0 publications found

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]

ENSG00000227757 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.22793597).
• BS2: High AC in GnomAdExome4 at 6 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.283C>G	p.Arg95Gly	missense	Exon 1 of 1	NP_620450.2	Q8TAK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OLIG1	ENST00000382348.2	TSL:6 MANE Select	c.283C>G	p.Arg95Gly	missense	Exon 1 of 1	ENSP00000371785.1	Q8TAK6
	ENSG00000227757	ENST00000454622.2	TSL:2	n.201+375G>C		intron	N/A
	ENSG00000227757	ENST00000777421.1		n.91+375G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000103 AC: 1 AN: 97058 AF XY: 0.0000183

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1348032 Hom.: 0 Cov.: 33 AF XY: 0.00000301 AC XY: 2 AN XY: 664882

African (AFR) AF: 0.00 AC: 0 AN: 27302

American (AMR) AF: 0.00 AC: 0 AN: 30196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23636

East Asian (EAS) AF: 0.00 AC: 0 AN: 30884

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4798

European-Non Finnish (NFE) AF: 0.00000376 AC: 4 AN: 1062488

Other (OTH) AF: 0.0000179 AC: 1 AN: 55992

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151952 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74212

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	0.81	L
PhyloP100		-0.13
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.24		Loss of loop (P = 0.0112)
MVP		0.91
MPC		2.0
ClinPred		0.13	T
GERP RS		1.1
PromoterAI		0.055	Neutral
Varity_R		0.23
gMVP		0.90
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1170507348; hg19: chr21-34442835;