rs7651166

Positions:

• chr3-181305520-C-T

Variant summary

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

The ENST00000493521.5(SOX2-OT):​n.218+129937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,112 control chromosomes in the GnomAD database, including 1,684 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 0.093 (1684 hom., cov: 32)
• Consequence: SOX2-OT ENST00000493521.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX2-OT	NR_075091.1	n.218+129937C>T		intron_variant
SOX2-OT	NR_075092.1	n.218+129937C>T		intron_variant
SOX2-OT	NR_075093.1	n.194+129937C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000460739.5	n.213+129937C>T		intron_variant		4
SOX2-OT	ENST00000469278.5	n.194+129937C>T		intron_variant		4
SOX2-OT	ENST00000493116.6	n.333+129937C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14112 AN: 151994 Hom.: 1681 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.00686

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0930 AC: 14139 AN: 152112 Hom.: 1684 Cov.: 32 AF XY: 0.0926 AC XY: 6889 AN XY: 74380

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00687

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0388 Hom.: 135

Bravo AF: 0.104

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7651166; hg19: chr3-181023308;