3-181194230-C-G

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+18647C>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 0.768 in 152,040 control chromosomes in the GnomAD database, including 46,138 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 0.77 (46138 hom., cov: 31)
• Consequence: SOX2-OT NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

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 (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2-OT	NR_075091.1	n.218+18647C>G		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075092.1	n.218+18647C>G		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075093.1	n.194+18647C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.272+18647C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116678 AN: 151922 Hom.: 46109 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.768 AC: 116750 AN: 152040 Hom.: 46138 Cov.: 31 AF XY: 0.771 AC XY: 57315 AN XY: 74350

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.786

Alfa AF: 0.814 Hom.: 6037

Bravo AF: 0.755

Asia WGS AF: 0.828 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.23
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2567661; hg19: chr3-180912018;