rs9290718

Positions:

• chr3-181296054-C-T

Variant summary

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

The NR_075091.1(SOX2-OT):​n.218+120471C>T 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 0.0625 in 151,826 control chromosomes in the GnomAD database, including 816 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 0.062 (816 hom., cov: 32)
• Consequence: SOX2-OT NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX2-OT	NR_075091.1	n.218+120471C>T		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075092.1	n.218+120471C>T		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075093.1	n.194+120471C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.272+120471C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9452 AN: 151708 Hom.: 811 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00636

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0625 AC: 9487 AN: 151826 Hom.: 816 Cov.: 32 AF XY: 0.0598 AC XY: 4439 AN XY: 74204

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.00636

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0508

Alfa AF: 0.0366 Hom.: 70

Bravo AF: 0.0692

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
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: rs9290718; hg19: chr3-181013842;