3-181063312-C-T

Variant names:

• chr3-181063312-C-T
• rs4854912
• ENST00000460739.6:n.102+6526C>T

Variant summary

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

The ENST00000461063.7(SOX2-OT):​n.239-25565C>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 ENST00000461063.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461063.7. 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_075091.1		n.107+6526C>T		intron	N/A
	SOX2-OT	NR_075092.1		n.107+6526C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000460739.6	TSL:4	n.102+6526C>T		intron	N/A
	SOX2-OT	ENST00000461063.7	TSL:3	n.239-25565C>T		intron	N/A
	SOX2-OT	ENST00000493116.6	TSL:4	n.223-25565C>T		intron	N/A

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

African (AFR) AF: 0.0574 AC: 2379 AN: 41426

American (AMR) AF: 0.175 AC: 2667 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5150

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4810

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10528

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.200 AC: 13565 AN: 67954

Other (OTH) AF: 0.193 AC: 405 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.43

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4854912;

hg19: chr3-180781100;