rs12497248

Positions:

• chr3-181706627-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NR_075091.1(SOX2-OT):​n.782+6744C>G variant causes a intron, non coding transcript 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 NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SOX2-OT	NR_075091.1	n.782+6744C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.836+6744C>G		intron_variant, non_coding_transcript_variant		5
	ENST00000688048.1	n.192+87G>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0519

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.174

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12497248; hg19: chr3-181424415;