3-181063312-C-T

Variant names:

• chr3-181063312-C-T
• rs4854912
• ENST00000460739.5:n.102+6526C>T

Variant summary

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

The ENST00000461063.6(SOX2-OT):​n.220-25565C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,910 control chromosomes in the GnomAD database, including 2,220 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 0.15 (2220 hom., cov: 32)
• Consequence: SOX2-OT ENST00000461063.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_075091.1	n.107+6526C>T		intron_variant	Intron 1 of 7
SOX2-OT	NR_075092.1	n.107+6526C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000460739.5	n.102+6526C>T		intron_variant	Intron 1 of 4	4
SOX2-OT	ENST00000461063.6	n.220-25565C>T		intron_variant	Intron 2 of 3	3
SOX2-OT	ENST00000493116.6	n.223-25565C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23516 AN: 151794 Hom.: 2215 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.155 AC: 23535 AN: 151910 Hom.: 2220 Cov.: 32 AF XY: 0.153 AC XY: 11376 AN XY: 74234

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.193

Alfa AF: 0.111 Hom.: 227

Bravo AF: 0.153

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4854912; hg19: chr3-180781100;