chr3-181754608-T-C

Variant names:

• chr3-181754608-T-C
• rs6443762
• ENST00000498226.6:n.289-36065T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498226.6(SOX2-OT):​n.289-36065T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,650 control chromosomes in the GnomAD database, including 19,231 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 0.50 (19231 hom., cov: 33)
• Consequence: SOX2-OT ENST00000498226.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498226.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000498226.6	TSL:4	n.289-36065T>C		intron	N/A
	SOX2-OT	ENST00000593330.2	TSL:3	n.355+54725T>C		intron	N/A
	SOX2-OT	ENST00000595084.3	TSL:5	n.286+54725T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75545 AN: 151534 Hom.: 19208 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.499 AC: 75621 AN: 151650 Hom.: 19231 Cov.: 33 AF XY: 0.505 AC XY: 37399 AN XY: 74086

African (AFR) AF: 0.566 AC: 23374 AN: 41332

American (AMR) AF: 0.559 AC: 8521 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3466

East Asian (EAS) AF: 0.743 AC: 3815 AN: 5134

South Asian (SAS) AF: 0.555 AC: 2676 AN: 4822

European-Finnish (FIN) AF: 0.526 AC: 5512 AN: 10486

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29067 AN: 67854

Other (OTH) AF: 0.463 AC: 975 AN: 2108

Alfa AF: 0.474 Hom.: 2216

Bravo AF: 0.509

Asia WGS AF: 0.648 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.38
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs6443762; hg19: chr3-181472396;