rs9290727

Variant names:

• chr3-181702830-T-C
• rs9290727
• ENST00000466034.7:n.349+2947T>C

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+2947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,130 control chromosomes in the GnomAD database, including 9,869 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 0.28 (9869 hom., cov: 32)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.767+2947T>C		intron_variant	Intron 3 of 4
SOX2-OT	NR_075089.1	n.767+2947T>C		intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1	n.482-36739T>C		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+2947T>C		intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6	n.482-36739T>C		intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6	n.593+2947T>C		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41805 AN: 152012 Hom.: 9845 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.275 AC: 41885 AN: 152130 Hom.: 9869 Cov.: 32 AF XY: 0.264 AC XY: 19651 AN XY: 74402

African (AFR) AF: 0.642 AC: 26602 AN: 41452

American (AMR) AF: 0.151 AC: 2304 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4826

European-Finnish (FIN) AF: 0.0964 AC: 1023 AN: 10608

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10264 AN: 67982

Other (OTH) AF: 0.228 AC: 482 AN: 2114

Alfa AF: 0.183 Hom.: 1875

Bravo AF: 0.294

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9290727; hg19: chr3-181420618;