3-181749022-G-T

Variant names:

• chr3-181749022-G-T
• rs4855037
• ENST00000498226.6:n.289-41651G>T

Variant summary

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

The ENST00000593330.2(SOX2-OT):​n.355+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 ENST00000593330.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000593330.2. 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.289-41651G>T		intron	N/A
	SOX2-OT	ENST00000593330.2	TSL:3	n.355+49139G>T		intron	N/A
	SOX2-OT	ENST00000595084.3	TSL:5	n.286+49139G>T		intron	N/A

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

African (AFR) AF: 0.576 AC: 23908 AN: 41472

American (AMR) AF: 0.562 AC: 8586 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.746 AC: 3857 AN: 5170

South Asian (SAS) AF: 0.539 AC: 2601 AN: 4824

European-Finnish (FIN) AF: 0.529 AC: 5588 AN: 10560

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

European-Non Finnish (NFE) AF: 0.426 AC: 28942 AN: 67968

Other (OTH) AF: 0.465 AC: 981 AN: 2108

Alfa AF: 0.453 Hom.: 46551

Bravo AF: 0.511

Asia WGS AF: 0.644 AC: 2240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.65
DANN	Benign	0.72
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs4855037; hg19: chr3-181466810;