rs1059004

chr21-33028155-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005806.4(OLIG2):c.*321C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 316,352 control chromosomes in the GnomAD database, including 36,313 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (15280 hom., cov: 31)
  • Exomes 𝑓: 0.49 (21033 hom.)
• Consequence: OLIG2 NM_005806.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

Genes affected

OLIG2 (HGNC:9398): (oligodendrocyte transcription factor 2) This gene encodes a basic helix-loop-helix transcription factor which is expressed in oligodendroglial tumors of the brain. The protein is an essential regulator of ventral neuroectodermal progenitor cell fate. The gene is involved in a chromosomal translocation t(14;21)(q11.2;q22) associated with T-cell acute lymphoblastic leukemia. Its chromosomal location is within a region of chromosome 21 which has been suggested to play a role in learning deficits associated with Down syndrome. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLIG2	NM_005806.4	c.*321C>A		3_prime_UTR_variant	2/2	ENST00000382357.4
OLIG2	XM_005260908.2	c.*321C>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLIG2	ENST00000382357.4	c.*321C>A		3_prime_UTR_variant	2/2	1	NM_005806.4	P1
	ENST00000454622.2	n.201+42749G>T		intron_variant, non_coding_transcript_variant		2
OLIG2	ENST00000333337.3	c.*321C>A		3_prime_UTR_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62642 AN: 151856 Hom.: 15278 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.486 AC: 79864 AN: 164378 Hom.: 21033 Cov.: 2 AF XY: 0.490 AC XY: 39225 AN XY: 80084

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.617

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.412 AC: 62650 AN: 151974 Hom.: 15280 Cov.: 31 AF XY: 0.411 AC XY: 30525 AN XY: 74288

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.445

Alfa AF: 0.505 Hom.: 7375

Bravo AF: 0.398

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.75
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs1059004; hg19: chr21-34400463;