rs7610679

Positions:

• chr3-181742799-C-T

Variant summary

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

The ENST00000498731.6(SOX2-OT):​n.3879C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 141,980 control chromosomes in the GnomAD database, including 27,584 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 0.62 (27583 hom., cov: 21)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: SOX2-OT ENST00000498731.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.944+27507C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.620 AC: 87979 AN: 141886 Hom.: 27549 Cov.: 21

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.461

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 ASJ exome AF: 1.00

GnomAD4 genome AF: 0.620 AC: 88054 AN: 141978 Hom.: 27583 Cov.: 21 AF XY: 0.624 AC XY: 42962 AN XY: 68810

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.587

Alfa AF: 0.581 Hom.: 33741

Bravo AF: 0.628

Asia WGS AF: 0.640 AC: 2153 AN: 3368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.2
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7610679; hg19: chr3-181460587;