3-181717360-A-G

Variant summary

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

The NR_075091.1(SOX2-OT):n.890+2068A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,592 control chromosomes in the GnomAD database, including 8,397 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 0.32 (8397 hom., cov: 30)
• Consequence: SOX2-OT NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2-OT	NR_075091.1	n.890+2068A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.944+2068A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48075 AN: 151474 Hom.: 8397 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.317 AC: 48090 AN: 151592 Hom.: 8397 Cov.: 30 AF XY: 0.329 AC XY: 24393 AN XY: 74050

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.273

Alfa AF: 0.269 Hom.: 6188

Bravo AF: 0.318

Asia WGS AF: 0.481 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4575941; hg19: chr3-181435148;