3-181749022-G-T

Variant names:

• chr3-181749022-G-T
• rs4855037
• ENST00000498226.5:n.287-41651G>T

Variant summary

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

The ENST00000593330.1(SOX2-OT):​n.44+49139G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,050 control chromosomes in the GnomAD database, including 19,519 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 (19519 hom., cov: 32)
• Consequence: SOX2-OT ENST00000593330.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 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.287-41651G>T		intron_variant	Intron 2 of 2	4
SOX2-OT	ENST00000593330.1	n.44+49139G>T		intron_variant	Intron 1 of 1	3
SOX2-OT	ENST00000595084.3	n.286+49139G>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76079 AN: 151932 Hom.: 19497 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.501 AC: 76156 AN: 152050 Hom.: 19519 Cov.: 32 AF XY: 0.508 AC XY: 37715 AN XY: 74300

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.465

Alfa AF: 0.434 Hom.: 24940

Bravo AF: 0.511

Asia WGS AF: 0.644 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.65
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4855037; hg19: chr3-181466810;