rs6443761

Variant names:

• chr3-181754604-T-A
• rs6443761
• ENST00000498226.5:n.287-36069T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-181754604-T-A
• chr3-181754604-T-G

Variant summary

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

The ENST00000593330.1(SOX2-OT):​n.44+54721T>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 ENST00000593330.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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=-0.9).
• 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	ENST00000498226.5	n.287-36069T>A		intron_variant	Intron 2 of 2	4
SOX2-OT	ENST00000593330.1	n.44+54721T>A		intron_variant	Intron 1 of 1	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

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.462

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6443761; hg19: chr3-181472392;