3-181749188-G-T

Variant names:

• chr3-181749188-G-T
• rs1558798
• ENST00000498226.6:n.289-41485G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498226.6(SOX2-OT):​n.289-41485G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,046 control chromosomes in the GnomAD database, including 13,586 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 0.42 (13586 hom., cov: 33)
• Consequence: SOX2-OT ENST00000498226.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 5 publications found

Genes affected

SOX2-OT (HGNC:20209): (SOX2 overlapping transcript) This gene produces alternatively spliced long non-coding RNAs. These RNAs were observed to be upregulated in tumor cells and positively correlated to expression of the SRY-box 2 gene. Overexpression of these transcripts may promote cell proliferation. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498226.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000498226.6	TSL:4	n.289-41485G>T		intron	N/A
	SOX2-OT	ENST00000593330.2	TSL:3	n.355+49305G>T		intron	N/A
	SOX2-OT	ENST00000595084.3	TSL:5	n.286+49305G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63437 AN: 151926 Hom.: 13581 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63489 AN: 152046 Hom.: 13586 Cov.: 33 AF XY: 0.423 AC XY: 31440 AN XY: 74316

African (AFR) AF: 0.490 AC: 20334 AN: 41456

American (AMR) AF: 0.442 AC: 6756 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2613 AN: 5168

South Asian (SAS) AF: 0.419 AC: 2015 AN: 4808

European-Finnish (FIN) AF: 0.484 AC: 5112 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24643 AN: 67974

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.375 Hom.: 15217

Bravo AF: 0.423

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.056

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1558798; hg19: chr3-181466976;