chr3-181754604-T-A

Variant names:

• chr3-181754604-T-A
• rs6443761
• ENST00000498226.6:n.289-36069T>A

Variant summary

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

The ENST00000498226.6(SOX2-OT):​n.289-36069T>A 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 151,622 control chromosomes in the GnomAD database, including 19,233 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 (19233 hom., cov: 33)
• Consequence: SOX2-OT ENST00000498226.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000498226.6	n.289-36069T>A		intron_variant	Intron 2 of 2	4
SOX2-OT	ENST00000593330.2	n.355+54721T>A		intron_variant	Intron 2 of 2	3
SOX2-OT	ENST00000595084.3	n.286+54721T>A		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75546 AN: 151504 Hom.: 19210 Cov.: 33

Gnomad AFR AF: 0.566

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: 0.429

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: 75623 AN: 151622 Hom.: 19233 Cov.: 33 AF XY: 0.505 AC XY: 37416 AN XY: 74088

African (AFR) AF: 0.566 AC: 23377 AN: 41316

American (AMR) AF: 0.559 AC: 8520 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3466

East Asian (EAS) AF: 0.743 AC: 3818 AN: 5136

South Asian (SAS) AF: 0.555 AC: 2676 AN: 4824

European-Finnish (FIN) AF: 0.526 AC: 5517 AN: 10488

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

European-Non Finnish (NFE) AF: 0.428 AC: 29060 AN: 67828

Other (OTH) AF: 0.462 AC: 976 AN: 2112

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.35
PhyloP100		-0.77

Splicing

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

Other links and lift over

dbSNP: rs6443761; hg19: chr3-181472392;