rs4855026

chr3-181409174-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_075091.1(SOX2-OT):n.219-154546G>A variant causes a intron, non coding transcript 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 NR_075091.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX2-OT	NR_075091.1	n.219-154546G>A		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075092.1	n.219-154546G>A		intron_variant, non_coding_transcript_variant
SOX2-OT	NR_075093.1	n.195-154546G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX2-OT	ENST00000626948.3	n.273-154546G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000663941.1	n.528+12160C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0994

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.137

Alfa AF: 0.139 Hom.: 3039

Bravo AF: 0.134

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.25
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4855026; hg19: chr3-181126962;