3-181717360-A-G

Variant names:

• chr3-181717360-A-G
• rs4575941
• ENST00000466034.7:n.349+17477A>G

Variant summary

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

The ENST00000466034.7(SOX2-OT):​n.349+17477A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,592 control chromosomes in the GnomAD database, including 8,397 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 (8397 hom., cov: 30)
• Consequence: SOX2-OT ENST00000466034.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 12 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466034.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	NR_004053.3		n.875+2068A>G		intron	N/A
	SOX2-OT	NR_075089.1		n.767+17477A>G		intron	N/A
	SOX2-OT	NR_075090.1		n.482-22209A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000466034.7	TSL:1	n.349+17477A>G		intron	N/A
	SOX2-OT	ENST00000476964.6	TSL:1	n.482-22209A>G		intron	N/A
	SOX2-OT	ENST00000491282.6	TSL:1	n.593+17477A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48075 AN: 151474 Hom.: 8397 Cov.: 30

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.317 AC: 48090 AN: 151592 Hom.: 8397 Cov.: 30 AF XY: 0.329 AC XY: 24393 AN XY: 74050

African (AFR) AF: 0.327 AC: 13490 AN: 41272

American (AMR) AF: 0.399 AC: 6080 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3236 AN: 5152

South Asian (SAS) AF: 0.327 AC: 1560 AN: 4772

European-Finnish (FIN) AF: 0.432 AC: 4518 AN: 10462

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17670 AN: 67904

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.283 Hom.: 18644

Bravo AF: 0.318

Asia WGS AF: 0.481 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.11

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4575941;

hg19: chr3-181435148;