3-181698818-T-G

Variant names:

• chr3-181698818-T-G
• rs13070015
• ENST00000476964.6:n.482-40751T>G

Variant summary

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

The ENST00000654649.1(SOX2-OT):​n.9T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,436 control chromosomes in the GnomAD database, including 30,833 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 0.62 (30831 hom., cov: 29)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: SOX2-OT ENST00000654649.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• Publications: 6 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]

ENSG00000239381 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000654649.1. 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.482-780T>G		intron	N/A
	SOX2-OT	NR_075089.1		n.482-780T>G		intron	N/A
	SOX2-OT	NR_075090.1		n.482-40751T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-40751T>G		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.308-780T>G		intron	N/A
	SOX2-OT	ENST00000498731.6	TSL:1	n.255-780T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93378 AN: 151294 Hom.: 30786 Cov.: 29

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.385 AC: 10 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.278 AC XY: 5 AN XY: 18

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.350 AC: 7 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.617 AC: 93485 AN: 151410 Hom.: 30831 Cov.: 29 AF XY: 0.612 AC XY: 45271 AN XY: 73916

African (AFR) AF: 0.851 AC: 35206 AN: 41388

American (AMR) AF: 0.579 AC: 8812 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1547 AN: 3448

East Asian (EAS) AF: 0.757 AC: 3878 AN: 5126

South Asian (SAS) AF: 0.268 AC: 1269 AN: 4742

European-Finnish (FIN) AF: 0.549 AC: 5730 AN: 10442

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35228 AN: 67734

Other (OTH) AF: 0.560 AC: 1178 AN: 2104

Alfa AF: 0.537 Hom.: 25405

Bravo AF: 0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.62

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: rs13070015;

hg19: chr3-181416606;