rs12487748

Variant names:

• chr3-181706444-T-A
• rs12487748
• ENST00000466034.7:n.349+6561T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-181706444-T-A
• chr3-181706444-T-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+6561T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,144 control chromosomes in the GnomAD database, including 1,820 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 0.15 (1820 hom., cov: 33)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.767+6561T>A		intron_variant	Intron 3 of 4
SOX2-OT	NR_075089.1	n.767+6561T>A		intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1	n.482-33125T>A		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+6561T>A		intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6	n.482-33125T>A		intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6	n.593+6561T>A		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22126 AN: 152026 Hom.: 1818 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.146 AC: 22143 AN: 152144 Hom.: 1820 Cov.: 33 AF XY: 0.139 AC XY: 10373 AN XY: 74384

African (AFR) AF: 0.205 AC: 8487 AN: 41482

American (AMR) AF: 0.105 AC: 1599 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4828

European-Finnish (FIN) AF: 0.0928 AC: 982 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9676 AN: 67992

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.0493 Hom.: 46

Bravo AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.53
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: rs12487748; hg19: chr3-181424232;