rs1558798

Variant names:

• chr3-181749188-G-T
• rs1558798
• ENST00000498226.5:n.287-41485G>T

Variant summary

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

The ENST00000593330.1(SOX2-OT):​n.44+49305G>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 ENST00000593330.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000498226.5	n.287-41485G>T		intron_variant	Intron 2 of 2	4
SOX2-OT	ENST00000593330.1	n.44+49305G>T		intron_variant	Intron 1 of 1	3
SOX2-OT	ENST00000595084.3	n.286+49305G>T		intron_variant	Intron 1 of 2	5

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.375

Alfa AF: 0.373 Hom.: 12949

Bravo AF: 0.423

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1558798; hg19: chr3-181466976;