3-181705066-A-G

Variant names:

• chr3-181705066-A-G
• rs4434184
• ENST00000466034.7:n.349+5183A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000466034.7(SOX2-OT):​n.349+5183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 150,450 control chromosomes in the GnomAD database, including 11,762 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 0.32 (11762 hom., cov: 30)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• 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]

ENSG00000289435 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX2-OT	NR_004053.3	n.767+5183A>G		intron_variant	Intron 3 of 4
SOX2-OT	NR_075089.1	n.767+5183A>G		intron_variant	Intron 3 of 3
SOX2-OT	NR_075090.1	n.482-34503A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX2-OT	ENST00000466034.7	n.349+5183A>G		intron_variant	Intron 1 of 2	1
SOX2-OT	ENST00000476964.6	n.482-34503A>G		intron_variant	Intron 2 of 2	1
SOX2-OT	ENST00000491282.6	n.593+5183A>G		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47446 AN: 150334 Hom.: 11724 Cov.: 30

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.316 AC: 47541 AN: 150450 Hom.: 11762 Cov.: 30 AF XY: 0.305 AC XY: 22438 AN XY: 73506

African (AFR) AF: 0.696 AC: 28073 AN: 40346

American (AMR) AF: 0.173 AC: 2626 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3464

East Asian (EAS) AF: 0.233 AC: 1193 AN: 5112

South Asian (SAS) AF: 0.0892 AC: 428 AN: 4796

European-Finnish (FIN) AF: 0.116 AC: 1211 AN: 10470

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.182 AC: 12355 AN: 67802

Other (OTH) AF: 0.274 AC: 572 AN: 2090

Alfa AF: 0.228 Hom.: 14634

Bravo AF: 0.342

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.72
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4434184; hg19: chr3-181422854;