chr3-181409174-G-A

Variant names:

• chr3-181409174-G-A
• rs4855026
• ENST00000460739.6:n.214-154546G>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.219-154546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,124 control chromosomes in the GnomAD database, including 1,376 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 0.13 (1376 hom., cov: 32)
• Consequence: SOX2-OT ENST00000493521.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	NR_075091.1		n.219-154546G>A		intron	N/A
	SOX2-OT	NR_075092.1		n.219-154546G>A		intron	N/A
	SOX2-OT	NR_075093.1		n.195-154546G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX2-OT	ENST00000460739.6	TSL:4	n.214-154546G>A		intron	N/A
	SOX2-OT	ENST00000469278.5	TSL:4	n.195-154546G>A		intron	N/A
	SOX2-OT	ENST00000493116.6	TSL:4	n.334-154546G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19860 AN: 152006 Hom.: 1377 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.131 AC: 19858 AN: 152124 Hom.: 1376 Cov.: 32 AF XY: 0.125 AC XY: 9321 AN XY: 74348

African (AFR) AF: 0.152 AC: 6295 AN: 41514

American (AMR) AF: 0.103 AC: 1567 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.0994 AC: 479 AN: 4820

European-Finnish (FIN) AF: 0.0898 AC: 951 AN: 10586

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9474 AN: 67986

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.139 Hom.: 4553

Bravo AF: 0.134

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.67
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs4855026; hg19: chr3-181126962;