rs733422

Variant names:

• chr3-181404262-C-A
• rs733422
• ENST00000460739.6:n.214-159458C>A

Variant summary

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

The ENST00000493521.5(SOX2-OT):​n.219-159458C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,958 control chromosomes in the GnomAD database, including 15,167 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 0.41 (15167 hom., cov: 32)
• Consequence: SOX2-OT ENST00000493521.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• 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]

ENSG00000241231 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493521.5. 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_075091.1		n.219-159458C>A		intron	N/A
	SOX2-OT	NR_075092.1		n.219-159458C>A		intron	N/A
	SOX2-OT	NR_075093.1		n.195-159458C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000460739.6	TSL:4	n.214-159458C>A		intron	N/A
	SOX2-OT	ENST00000469278.5	TSL:4	n.195-159458C>A		intron	N/A
	SOX2-OT	ENST00000493116.6	TSL:4	n.334-159458C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62672 AN: 151840 Hom.: 15161 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.413 AC: 62699 AN: 151958 Hom.: 15167 Cov.: 32 AF XY: 0.415 AC XY: 30853 AN XY: 74262

African (AFR) AF: 0.164 AC: 6802 AN: 41468

American (AMR) AF: 0.422 AC: 6444 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1777 AN: 5126

South Asian (SAS) AF: 0.386 AC: 1859 AN: 4810

European-Finnish (FIN) AF: 0.626 AC: 6609 AN: 10562

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36322 AN: 67926

Other (OTH) AF: 0.412 AC: 868 AN: 2108

Alfa AF: 0.469 Hom.: 7276

Bravo AF: 0.383

Asia WGS AF: 0.362 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		0.0090

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: rs733422;

hg19: chr3-181122050;