rs35788479

chr3-181708766-G-A

Variant summary

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

The NR_075091.1(SOX2-OT):n.783-6419G>A 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 0.195 in 152,042 control chromosomes in the GnomAD database, including 3,984 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 (3984 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOX2-OT NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2-OT	NR_075091.1	n.783-6419G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.837-6419G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000688048.1	n.82-1942C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29619 AN: 151924 Hom.: 3969 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.174

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.195 AC: 29673 AN: 152042 Hom.: 3984 Cov.: 33 AF XY: 0.187 AC XY: 13909 AN XY: 74356

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.0930

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.171

Alfa AF: 0.153 Hom.: 1920

Bravo AF: 0.205

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35788479; hg19: chr3-181426554;