chr3-181717502-T-A

Variant names:

• chr3-181717502-T-A
• rs4459940
• ENST00000466034.7:n.349+17619T>A

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+17619T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,890 control chromosomes in the GnomAD database, including 28,781 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 0.59 (28781 hom., cov: 31)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• 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]

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 (EAS) allele frequency at 95% confidence interval = 0.848 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	NR_004053.3		n.875+2210T>A		intron	N/A
	SOX2-OT	NR_075089.1		n.767+17619T>A		intron	N/A
	SOX2-OT	NR_075090.1		n.482-22067T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000466034.7	TSL:1	n.349+17619T>A		intron	N/A
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-22067T>A		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.593+17619T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88758 AN: 151772 Hom.: 28727 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.585 AC: 88869 AN: 151890 Hom.: 28781 Cov.: 31 AF XY: 0.588 AC XY: 43643 AN XY: 74220

African (AFR) AF: 0.855 AC: 35428 AN: 41424

American (AMR) AF: 0.561 AC: 8567 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.864 AC: 4457 AN: 5158

South Asian (SAS) AF: 0.433 AC: 2076 AN: 4796

European-Finnish (FIN) AF: 0.541 AC: 5697 AN: 10530

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29623 AN: 67932

Other (OTH) AF: 0.509 AC: 1074 AN: 2112

Alfa AF: 0.340 Hom.: 816

Bravo AF: 0.601

Asia WGS AF: 0.686 AC: 2382 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	0.41
DANN	Benign	0.68
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs4459940; hg19: chr3-181435290;