3-181705814-C-G

Variant names:

• chr3-181705814-C-G
• rs12496378
• ENST00000466034.7:n.349+5931C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466034.7(SOX2-OT):​n.349+5931C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,130 control chromosomes in the GnomAD database, including 1,710 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 0.12 (1710 hom., cov: 32)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 5 publications found

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]

ENSG00000289435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466034.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	NR_004053.3		n.767+5931C>G		intron	N/A
	SOX2-OT	NR_075089.1		n.767+5931C>G		intron	N/A
	SOX2-OT	NR_075090.1		n.482-33755C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000466034.7	TSL:1	n.349+5931C>G		intron	N/A
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-33755C>G		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.593+5931C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18800 AN: 152012 Hom.: 1712 Cov.: 32

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.124 AC: 18795 AN: 152130 Hom.: 1710 Cov.: 32 AF XY: 0.129 AC XY: 9606 AN XY: 74350

African (AFR) AF: 0.0295 AC: 1227 AN: 41532

American (AMR) AF: 0.189 AC: 2894 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2052 AN: 5154

South Asian (SAS) AF: 0.0926 AC: 446 AN: 4816

European-Finnish (FIN) AF: 0.210 AC: 2219 AN: 10572

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9299 AN: 67986

Other (OTH) AF: 0.0994 AC: 210 AN: 2112

Alfa AF: 0.138 Hom.: 224

Bravo AF: 0.119

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs12496378; hg19: chr3-181423602;