3-181717360-A-G

Variant names:

• chr3-181717360-A-G
• rs4575941
• ENST00000466034.7:n.349+17477A>G

Variant summary

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

The ENST00000466034.7(SOX2-OT):​n.349+17477A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,592 control chromosomes in the GnomAD database, including 8,397 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 0.32 (8397 hom., cov: 30)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.875+2068A>G		intron_variant	Intron 4 of 4
SOX2-OT	NR_075089.1	n.767+17477A>G		intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1	n.482-22209A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000466034.7	n.349+17477A>G		intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6	n.482-22209A>G		intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6	n.593+17477A>G		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48075 AN: 151474 Hom.: 8397 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.317 AC: 48090 AN: 151592 Hom.: 8397 Cov.: 30 AF XY: 0.329 AC XY: 24393 AN XY: 74050

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.273

Alfa AF: 0.269 Hom.: 6188

Bravo AF: 0.318

Asia WGS AF: 0.481 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4575941; hg19: chr3-181435148;