rs2718771

chr3-181264288-A-Cchr3-181264288-A-T

Variant summary

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

The NR_075091.1(SOX2-OT):n.218+88705A>C 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 0.867 in 151,896 control chromosomes in the GnomAD database, including 57,237 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 0.87 (57237 hom., cov: 30)
• Consequence: SOX2-OT NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2-OT	NR_075091.1	n.218+88705A>C		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075092.1	n.218+88705A>C		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075093.1	n.194+88705A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.272+88705A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131638 AN: 151778 Hom.: 57190 Cov.: 30

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.867 AC: 131741 AN: 151896 Hom.: 57237 Cov.: 30 AF XY: 0.871 AC XY: 64657 AN XY: 74238

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.879

Alfa AF: 0.871 Hom.: 7178

Bravo AF: 0.870

Asia WGS AF: 0.957 AC: 3326 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.4
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2718771; hg19: chr3-180982076;