rs6517137

chr21-33028471-T-C

Variant summary

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

The NM_005806.4(OLIG2):c.*637T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 233,444 control chromosomes in the GnomAD database, including 1,585 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 0.11 (1135 hom., cov: 33)
  • Exomes 𝑓: 0.096 (450 hom.)
• Consequence: OLIG2 NM_005806.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OLIG2	NM_005806.4	c.*637T>C		3_prime_UTR_variant	2/2	ENST00000382357.4
OLIG2	XM_005260908.2	c.*637T>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OLIG2	ENST00000382357.4	c.*637T>C		3_prime_UTR_variant	2/2	1	NM_005806.4	P1
	ENST00000454622.2	n.201+42433A>G		intron_variant, non_coding_transcript_variant		2
OLIG2	ENST00000333337.3	c.*637T>C		3_prime_UTR_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17102 AN: 152010 Hom.: 1127 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0990

GnomAD4 exome AF: 0.0965 AC: 7846 AN: 81314 Hom.: 450 Cov.: 0 AF XY: 0.0971 AC XY: 3674 AN XY: 37838

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0861

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.0937

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0810

Gnomad4 OTH exome AF: 0.0959

GnomAD4 genome AF: 0.113 AC: 17127 AN: 152130 Hom.: 1135 Cov.: 33 AF XY: 0.116 AC XY: 8597 AN XY: 74372

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0847 Hom.: 986

Bravo AF: 0.110

Asia WGS AF: 0.170 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.64

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: rs6517137; hg19: chr21-34400779;