rs12497248

Variant names:

• chr3-181706627-C-G
• rs12497248
• ENST00000466034.7:n.349+6744C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000466034.7(SOX2-OT):​n.349+6744C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,074 control chromosomes in the GnomAD database, including 4,144 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 0.20 (4144 hom., cov: 33)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• 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]

ENSG00000289435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.767+6744C>G		intron_variant	Intron 3 of 4
SOX2-OT	NR_075089.1	n.767+6744C>G		intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1	n.482-32942C>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+6744C>G		intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6	n.482-32942C>G		intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6	n.593+6744C>G		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30082 AN: 151956 Hom.: 4126 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.198 AC: 30146 AN: 152074 Hom.: 4144 Cov.: 33 AF XY: 0.190 AC XY: 14153 AN XY: 74350

African (AFR) AF: 0.382 AC: 15846 AN: 41436

American (AMR) AF: 0.128 AC: 1949 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3470

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

South Asian (SAS) AF: 0.0519 AC: 250 AN: 4816

European-Finnish (FIN) AF: 0.0949 AC: 1003 AN: 10570

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9828 AN: 67988

Other (OTH) AF: 0.174 AC: 368 AN: 2114

Alfa AF: 0.167 Hom.: 340

Bravo AF: 0.208

Asia WGS AF: 0.0450 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.74
PhyloP100		2.2
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: rs12497248; hg19: chr3-181424415;